Oncotarget: Recent Episodes
Oncotarget Podcast
Oncotarget is a peer-reviewed, open-access biomedical journal dedicated to publishing high-quality, primarily oncology-focused research.
Lung cancer remains one of the leading causes of cancer-related deaths worldwide. Although precision medicine has improved outcomes for many patients, certain rare genetic mutations are still poorly understood, particularly in regions with limited access to genomic testing. Such mutations involve the HER2 gene, better known for its role in breast cancer but also implicated in a small subset of lung cancers.HER2 mutations are found in approximately 2–4% of non-small cell lung cancer (NSCLC) cases and create unique challenges. These tumors can vary significantly in how they appear under a microscope and in how they respond to treatment. Adding to the complexity, most diagnostic and treatment guidelines are based on research from high-income countries, which may not reflect the genetic diversity seen in other parts of the world.To help close this knowledge gap, researchers in Northeastern Brazil conducted one of the first detailed investigations into HER2-mutated NSCLC in Latin America. Their study, recently published in Volume 16 of Oncotarget, reveals a complex and often overlooked form of the disease, highlighting the need for broader access to targeted therapies in underserved populations.Full blog - https://www.oncotarget.org/2025/10/08/new-insights-into-her2-mutated-non-small-cell-lung-cancer-in-brazil/Paper DOI - https://doi.org/10.18632/oncotarget.28737Correspondence to - Fabio Tavora - stellacpak@outlook.comAbstract video - https://www.youtube.com/watch?v=hr5R9iDBFFISign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28737Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, HER2 mutation, NSCLC, lung cancer, targeted therapy, genomic profilingTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY – October 8, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on October 6, 2025, titled “ACTM-838, a novel systemically delivered bacterial immunotherapy that enriches in solid tumors and delivers IL-15/IL-15Rα and STING payloads to engage innate and adaptive immunity in the TME and enable a durable anti-tumor immune response.”In this study, led by first author Kyle R. Cron and corresponding author Akshata R. Udyavar, researchers from Actym Therapeutics developed a new form of bacterial immunotherapy called ACTM-838. This treatment safely delivers immune-activating proteins directly to solid tumors. The approach may offer a new option for cancer patients whose solid tumors are resistant to current immunotherapies.Solid tumors often suppress the immune system, making it difficult for treatments like immune checkpoint inhibitors to work effectively. ACTM-838 was designed to overcome this challenge by targeting phagocytic immune cells within the tumor microenvironment (TME). Once inside the tumor, the therapy delivers two immune-stimulating components: IL-15/IL-15Rα and a modified version of STING. Both are known to activate the body’s innate and adaptive immune responses. This combination of immune-stimulating proteins helps shift the TME from immune-suppressive to immune-permissive, enabling the body’s natural defenses to fight the cancer.“STACT is a modular, genetically engineered live attenuated S. Typhimurium bacterial platform that enables tissue-specific localization and cell-targeted delivery of large, multiplexed payloads via systemic administration.”The study highlights how ACTM-838, built on a specially modified strain of Salmonella Typhimurium, safely targets tumors and avoids healthy tissue after intravenous injection. This targeted delivery reduces the risk of side effects while ensuring the immune-boosting agents reach their intended location. Importantly, ACTM-838 also showed significantly reduced inflammatory toxicity compared to its parent bacterial strain, which had previously presented challenges in clinical use.In preclinical tests, ACTM-838 shrank tumors and prevented their recurrence after treatment. Mice that were cured of tumors resisted re-injection with cancer cells, suggesting the development of long-lasting immune memory. The therapy also showed strong synergy with anti-PD1 drugs, a widely used class of cancer treatments, further improving outcomes in both treatment-resistant and responsive tumor models.Researchers also found that ACTM-838 changed the composition of immune cells within the tumor. It increased beneficial cells like cytotoxic T-cells and antigen-presenting macrophages, while reducing suppressive cell types such as regulatory T-cells and exhausted T-cells. These effects were confirmed through genetic analysis and cellular studies, pointing to a broad and coordinated immune response.This study offers proof-of-concept that live bacterial therapy can safely and effectively deliver gene-based immune modulators directly to tumors. With ACTM-838 now being tested in a Phase I clinical trial, the findings offer a new direction for cancer treatment strategies that activate the body’s own immune system, particularly in difficult-to-treat cases where other therapies fail.DOI - https://doi.org/10.18632/oncotarget.28769Correspondence to - Akshata R. Udyavar - akshata.udyavar@pfizer.comAbstract video - https://www.youtube.com/watch?v=fr5OR3tvC_IFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - October 1, 2025 – Oncotarget is proud to announce that its Editor-in-Chief, Wafik S. El-Deiry, MD, PhD, FACP, will chair the WIN Symposium as the Oncology Track of the Advancing Precision Medicine (APM) Annual Conference held October 3–4, 2025, at the Pennsylvania Convention Center in Philadelphia.The WIN Consortium annual symposium featured as the Oncology Track of the APM Annual Conference 2025 unites global leaders in oncology, translational science, and precision medicine. This year’s program features keynote lectures, multi-track sessions– WIN Symposium, Multi-Omics Integration and Precision Medicine Outside of Oncology– and networking opportunities designed to accelerate the translation of research into clinical practice.Highlights include:--A keynote at opening of the WIN Symposium in Philadelphia by William G. Kaelin, Jr., MD — 2019 Nobel Laureate.--Other luminaries in Oncology are speaking, including AACR President Lillian Siu, MD and AACR President-Elect Keith Flaherty, MD along with internationally recognized leaders in precision oncology.--A world-class precision oncology molecular tumor board and oral presentations from the most competitive abstracts are part of the program.--Multi-omics and disease-specific tracks spanning oncology, neurology, cardiovascular disease, rare disease, and infectious disease.--Opportunities for collaboration among scientists, clinicians, industry innovators, and policymakers.Registration is still open. Attendance is free for students, academic/government/non-profit participants, healthcare providers, and investors. The event provides CME credits. For full program details, visit the APM Annual Conference website.About WIN Consortium:WIN Consortium is a non-profit association headquartered in France. WIN was the first consortium that assembled all stakeholders of cancer care, from academia, industry, and patient advocates to work together across the globe. The WIN network assembles 34 world-class academic medical centers, industries, research organizations and patient advocates spanning 18 countries and 5 continents, aligned to launch trials to bolster Precision Oncology across the world. It was also the first organization to launch a N-of-One study using transcriptomics in addition to genomics to inform therapeutic choice in the WINTHER study.WIN is the organizer of the WIN symposia in Precision Oncology.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh
Colorectal cancer is one of the most common—and deadliest—cancers worldwide. Once it spreads and reaches the metastatic stage, treatment becomes far more difficult. Tumors can also behave very differently from one patient to another, especially after multiple rounds of therapy. Precision oncology is helping to overcome these challenges by enabling clinicians to analyze each tumor’s unique genetic profile and tailor treatment accordingly.This approach was recently highlighted in a case study published in Volume 16 of Oncotarget. The report detailed how a 62-year-old man with advanced colorectal cancer received a highly personalized treatment plan, developed by an international panel of experts, after completing all standard treatment options.Full blog - https://www.oncotarget.org/2025/09/24/precision-oncology-in-metastatic-colorectal-cancer-a-real-world-case-study/Paper DOI - https://doi.org/10.18632/oncotarget.28744Correspondence to - Shai Magidi - shai.magidi@winconsortium.orgAbstract video - https://www.youtube.com/watch?v=uWDtWNgpK7ASign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28744Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, precision oncology, molecular tumor board, colorectal carcinoma, cancer managementTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - September 24, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on September 22, 2025, titled “Loss of Trp53 results in a hypoactive T cell phenotype accompanied by reduced pro-inflammatory signaling in a syngeneic orthotopic mouse model of ovarian high-grade serous carcinoma.”In this study, led by first author Jacob Haagsma and corresponding author Trevor G. Shepherd from the Verspeeten Family Cancer Centre and Western University, Canada, researchers investigated how the loss of Trp53 – a critical tumor suppressor gene – affects immune responses in ovarian cancer. The team found that deleting Trp53 led to more aggressive tumor growth and a weaker immune response. These findings help explain why some ovarian tumors may be resistant to immunotherapy and point to new ways to improve treatment.High-grade serous ovarian carcinoma (HGSC) is a deadly cancer that is often diagnosed at a late stage. Immunotherapy, which enhances the body’s immune system to fight cancer, has shown limited effectiveness in treating this type of cancer. To better understand why, the researchers developed a mouse model that closely mimics human HGSC. They injected ovarian epithelial cells, with and without Trp53, into the fallopian tubes, the origin site of most ovarian cancers.“In this study, we developed a syngeneic model reflecting both the site of origin and the genotype of early HGSC disease by deleting Trp53 in mouse oviductal epithelial (OVE) cells.”Mice injected with cells lacking Trp53 developed faster-growing and more invasive tumors, reflecting how the disease typically progresses in humans. These tumors also had fewer active T cells, which are immune cells responsible for attacking cancer. Moreover, the T cells that were present appeared less capable of responding to the tumor, creating an immune environment that allowed cancer to grow uncontrolled.Further analysis revealed that tumor cells without Trp53 had reduced activity in genes related to inflammation. These changes were associated with lower levels of key proteins that normally help immune cells detect and attack tumor cells. When the researchers collected tumor cells from the abdominal fluid of the mice—a condition that simulates advanced-stage disease—they observed even lower immune signaling than before. This suggests that as the tumor spreads, it becomes better at evading the immune system.This study highlights how early genetic mutations can shape the interaction between tumors and the immune system. In particular, the loss of Trp53 appears to trigger a chain of events that weakens immune surveillance and accelerates tumor progression. These findings emphasize the need to consider both genetic mutations and the tumor environment when designing immunotherapies for ovarian cancer. Understanding how genes like Trp53 influence immune behavior may lead to more effective treatments and help identify which patients are most likely to benefit from immunotherapy.DOI - https://doi.org/10.18632/oncotarget.28768Correspondence to - Trevor G. Shepherd - tshephe6@uwo.caAbstract video - https://www.youtube.com/watch?v=WFQw0psuC3MSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28768Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
Immunotherapy is not usually effective against pancreatic cancer (PC), but a new study published in Oncotarget (Volume 16, 2025) highlights rare cases where it did help. These examples, though uncommon, may offer valuable insights for future treatment.Pancreatic Cancer and ImmunotherapyPancreatic cancer is often diagnosed at an advanced stage, which limits treatment options and contributes to its poor prognosis. While chemotherapy remains the standard treatment, it usually offers only modest benefits in terms of survival. Immunotherapy—an approach that activates the immune system to fight cancer—has been effective in other cancers but has shown limited success in PC.This is largely due to the tumor’s ability to suppress immune responses and create an environment that protects it from attack. Currently, these drugs are only approved for a small subset of patients whose tumors have a specific genetic feature called high microsatellite instability (MSI-high), found in just 1 to 2 percent of cases.The Study: Pancreatic Cancer Immunotherapy RespondersThe study, titled “Exceptional responders to immunotherapy in pancreatic cancer: A multi-institutional case series of a rare occurrence,” was led by first author Kavin Sugumar and corresponding author Jordan M. Winter, from University Hospitals Seidman Cancer Center. The researchers examined medical records from 14 patients with pancreatic ductal adenocarcinoma (PDAC) who had responded unexpectedly well to immune checkpoint inhibitors—drugs that help reactivate immune cells to attack cancer. The drugs included PD-1 inhibitors such as pembrolizumab and nivolumab, CTLA-4 inhibitors like ipilimumab, and agents targeting tumor-associated macrophages. To find these rare cases, the research team contacted 471 oncologists from 91 major U.S. cancer centers between 2020 and 2021.Full blog - https://www.oncotarget.org/2025/09/11/immunotherapy-response-in-pancreatic-cancer-what-a-new-study-reveals/Paper DOI - https://doi.org/10.18632/oncotarget.28739Correspondence to - Jordan M. Winter - jordan.winter@UHHospitals.orgAbstract video - https://www.youtube.com/watch?v=VeWTcuVmqgMSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28739Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, pancreatic adenocarcinoma, immunotherapy, exceptional responders, microsatellite instability, survivalTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY – August 29, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on August 29, 2025, titled “In vivo manipulation of the protein homeostasis network in rhabdomyosarcoma.”In this study led by first author Kristen Kwong and corresponding author Amit J. Sabnis from the Department of Pediatrics, Division of Oncology, University of California San Francisco, researchers discovered that disrupting the protein quality control system in cancer cells slows tumor growth in rhabdomyosarcoma (RMS), the most common pediatric soft tissue cancer. This finding points to a new strategy for treating high-risk childhood cancers that often resist current therapies.Rhabdomyosarcoma is a rare and aggressive cancer that primarily affects children and adolescents. Standard treatments like chemotherapy and radiation often have limited long-term success in high-risk cases. This study explored a different approach: targeting the cellular machinery that maintains protein quality, known as the proteostasis network. Cancer cells rely heavily on this system to survive stress caused by rapid growth and genetic instability.“To examine whether MAL3-101 or more drug-like proteostasis inhibitors represent a new therapeutic strategy for RMS, we screened proteostasis components that might recapitulate the effects of MAL3-101 in vivo.”The researchers first used a compound called MAL3-101 to disrupt protein control in RMS cells. They then identified which parts of the protein quality system were affected. Based on those findings, they searched for more drug-like compounds that could target the same pathways. They focused on a protein called p97, which plays a critical role in removing damaged or misfolded proteins. When they blocked p97 using a drug called CB-5083, the cancer cells could no longer manage internal stress and began to self-destruct. In both laboratory models and mice implanted with human RMS tumors, the treatment significantly slowed or stopped tumor growth. The drug triggered a stress response in the cells known as the unfolded protein response, which can lead to either recovery or programmed cell death.However, not all tumors responded the same way. Some resisted the treatment by activating a backup system called autophagy, which allows cells to recycle parts of themselves under stress. By comparing tumors that responded well to those that did not, the researchers found that higher autophagy activity could serve as a warning sign for resistance. This insight may help identify which patients are more likely to benefit from therapies that target protein quality control.While the results are promising, the drug’s effectiveness depended on the tumor’s genetic profile and how it handled stress. Combining p97 inhibition with other treatments or blocking alternative survival pathways like autophagy may improve outcomes. The researchers also noted the importance of developing safer and more targeted drugs to reduce side effects.This study opens new possibilities for personalized cancer treatment, particularly for children with aggressive or relapsed RMS. By weakening the systems that cancer cells depend on to survive, rather than only using toxic treatments to kill them, scientists aim to develop more effective and less harmful therapies for young patients.DOI - https://doi.org/10.18632/oncotarget.28764Correspondence to - Amit J. Sabnis - amit.sabnis@ucsf.eduVideo short - https://www.youtube.com/watch?v=YsdffTkXNRQTo learn more about Oncotarget, visit https://www.oncotarget.com.Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
Aiden Deacon from the University of Minnesota-Twin Cities, Minneapolis, discusses a research paper he co-authored that was published in Volume 16 of Oncotarget, titled “Dissecting the functional differences and clinical features of R-spondin family members in metastatic prostate cancer.”DOI - https://doi.org/10.18632/oncotarget.28758Correspondence to - Justin Hwang - jhwang@umn.eduVideo interview - https://www.youtube.com/watch?v=OXKhWWU1gnYAbstractThis study investigates the R-spondin family of genes (RSPO1/2/3/4), a group of secreted proteins that act as Wnt regulators, and their subsequent role in advanced prostate cancer (PC). When evaluating transcriptomic data from primary and metastatic PC patients, we found that alterations in RSPO2 were more prevalent than in other RSPO family members or Wnt-regulating genes APC and CTNNB1. Further, we found that RSPO2 alterations in PCs were significantly associated with worse disease-free survival. Through our in silico modeling, RSPO2 exhibited strong positive associations with genes regulating epithelial-mesenchymal transition (EMT) and double-negative prostate cancer (DNPC), but had negative correlations with androgen receptor (AR) and AR-associated genes. Furthermore, 3D modeling of RSPO2 revealed structural differences between itself and other RSPOs. In cell lines, RSPO2 overexpression caused up-regulation of EMT pathways, including EMT-regulatory transcription factors ZEB1, ZEB2, and TWIST1. Conversely, this was not observed when CTNNB1 was overexpressed in the same models. These findings highlight that, in PC, RSPO2 functions as a unique member of the R-spondin family by promoting genes and signaling pathways associated with aggressive PC, and RSPO2 amplifications are associated with poor outcomes in PC patients.Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28758Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, RSPO2, prostate cancer, Wnt signaling, genomics, therapeuticsAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality. While the development of targeted therapies has improved outcomes for many patients with EGFR-mutated NSCLC, those with rare EGFR variants often face limited treatment options, especially when the disease involves the central nervous system (CNS).A recent research paper, titled “Durable complete response in leptomeningeal disease of EGFR mutated non-small cell lung cancer to amivantamab, an EGFR-MET receptor bispecific antibody, after progressing on osimertinib” published in Volume 16 of Oncotarget, describes a patient with NSCLC harboring two uncommon EGFR mutations—G719A and A289V—who experienced a prolonged and clinically significant response to amivantamab monotherapy, after prior treatments had failed.Full blog - https://www.oncotarget.org/2025/08/26/amivantamab-monotherapy-in-rare-egfr-mutated-advanced-nsclc/Paper DOI - https://doi.org/10.18632/oncotarget.28730Correspondence to - Young Kwang Chae - young.chae@northwestern.eduVideo short - https://www.youtube.com/watch?v=UEiCz834a8cSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28730Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, amivantamab, monotherapy, rare EGFR mutation, NSCLC, leptomeningeal diseaseAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY – August 19, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on August 19, 2025, titled “The SCD1 inhibitor aramchol interacts with regorafenib to kill GI tumor cells in vitro and in vivo.”In this study, led by first authors Laurence Booth and Michael R. Booth, along with corresponding author Paul Dent from Virginia Commonwealth University, researchers investigated how aramchol, a drug originally developed for liver disease, works with the cancer drug regorafenib in gastrointestinal (GI) tumor cells. They found that the combination is effective, especially in tumor cells with a specific genetic variant. The combined approach offers a potential new strategy for treating liver and colon cancers.Gastrointestinal cancers, such as liver and colon cancer, are serious global health challenges. Regorafenib, already approved for cancer treatment, can have limited impact and frequently causes side effects. Aramchol, a drug developed to treat fatty liver disease, affects how cancer cells process fats and energy. In this study, researchers tested whether combining these two drugs could improve GI cancer treatment, both in cells and mouse models.The results showed that the drug combination killed liver and colorectal cancer cells more effectively than either drug alone. In animal models, mice with human liver tumors had slower tumor growth, without showing signs of weight loss or other toxicity. The researchers also found that aramchol and regorafenib work together to block important survival pathways inside cancer cells. This combination was especially effective in cells with a genetic variant called ATG16L1 T300, which is more common in people of African ancestry. The treatment triggered stress responses in the cancer cells and disrupted key proteins required for survival. It also activated autophagy, a natural recycling process that clears out damaged parts, eventually leading to cancer cell death.“Aramchol interacted with the multi-kinase inhibitors sorafenib, regorafenib or lenvatinib, to kill GI tumor cells, with regorafenib exhibiting the greatest effect.”Aramchol is currently in clinical trials for fatty liver disease and has a well-established safety profile, while regorafenib is already FDA-approved for cancer treatment. Together, their combination could advance fast into clinical testing for patients with GI cancers. However, researchers note that additional studies are needed to support the launch of early-phase clinical trials.Altogether, this study may offer a more effective and less toxic alternative to current treatments for GI cancers. It also highlights the role of genetic variants in shaping treatment response, suggesting that future therapies could be more precisely tailored to each patient’s unique genetic profile.DOI - https://doi.org/10.18632/oncotarget.28762Correspondence to - Paul Dent - paul.dent@vcuhealth.orgVideo short - https://www.youtube.com/watch?v=5saAqsqxi-QSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28762Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, macroautophagy, flux; ER stress, aramchol, regorafenibTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY – August 15, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on August 13, 2025, titled “Clinical and analytical validation of MI Cancer Seek®, a companion diagnostic whole exome and whole transcriptome sequencing-based comprehensive molecular profiling assay.”In this study, first authors Valeriy Domenyuk and Kasey Benson, along with corresponding author David Spetzler from Caris Life Sciences in Irving, Texas, introduce MI Cancer Seek, an FDA-approved test designed to deliver comprehensive tumor profiling. MI Cancer Seek demonstrated strong concordance with other FDA-approved companion diagnostics and serves as a powerful tool to guide treatment decisions in both adult and pediatric cancer patients.Cancer remains one of the most complex and diverse diseases to treat. With many targeted therapies currently FDA-approved, selecting the right one for a specific patient requires detailed genetic insights. MI Cancer Seek addresses this need by analyzing both DNA and RNA from a single tumor sample. The tool identifies key biomarkers linked to FDA-approved treatments for several major cancers, including breast, lung, colon, melanoma, and endometrial cancers.One of the most significant strengths of MI Cancer Seek is its ability to deliver accurate and reliable results from minimal tissue input (50 ng). Even when analyzing formalin-fixed paraffin-embedded samples, which are widely used but often degraded, the test maintained high levels of accuracy. It successfully detected important genetic alterations such as PIK3CA, EGFR, BRAF, and KRAS/NRAS mutations and measured tumor mutational burden (TMB) and microsatellite instability (MSI), both of which are key indicators for immunotherapy response.In clinical comparisons, the test achieved over 97% agreement with other FDA-approved diagnostic tools, confirming its reliability in detecting critical biomarkers. Notably, it showed near-perfect accuracy in identifying MSI status in colorectal and endometrial cancers. The researchers also demonstrated that the test maintains precision across different lab conditions and varying DNA input levels, confirming its robustness for routine clinical use.Beyond its role as a companion diagnostic, MI Cancer Seek incorporates additional features developed under its predecessor, MI Tumor Seek Hybrid. These include detection of homologous recombination deficiency, structural variants, and cancer-related viruses. It also includes advanced tools such as the Genomic Probability Score for identifying the tissue of origin in cancers of unknown primary, as well as a gene signature to guide first-line chemotherapy in colorectal cancer.“One limitation to be considered is the low PPA for ERBB2 CNA detection.”By offering deeper genetic insights from a single, small sample, MI Cancer Seek has the potential to streamline diagnostics, reduce testing costs, and connect patients to effective therapies more quickly. As precision medicine continues to expand, this assay stands out as a comprehensive and efficient solution for meeting the evolving needs of modern oncology.DOI - https://doi.org/10.18632/oncotarget.28761Correspondence to - David Spetzler - dspetzler@carisls.comVideo short - https://www.youtube.com/watch?v=D4hd2FxCYY8Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - August 13, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on July 29, 2025, titled “PCAIs stimulate MAPK, PI3K/AKT pathways and ROS-Mediated apoptosis in aromatase inhibitor-resistant breast cancer cells while disrupting actin filaments and focal adhesion.”In this study, led by first author Jassy Mary S. Lazarte and corresponding author Nazarius S. Lamango from Florida A&M University College of Pharmacy and Pharmaceutical Sciences, researchers investigated a new class of compounds called polyisoprenylated cysteinyl amide inhibitors (PCAIs) as a potential treatment for aromatase inhibitor (AI) therapy resistant breast cancer. Aromatase inhibitors are a common treatment for estrogen receptor-positive (ER+) breast cancer, but many patients eventually develop resistance, leaving fewer therapeutic options.The study focused on a PCAI compound called NSL-YHJ-2-27, which was tested in long-term letrozole-treated breast cancer cells (LTLT-Ca), an experimental model of AI therapy resistance. NSL-YHJ-2-27 activated two major signaling pathways, MAPK and PI3K/AKT. Although these pathways typically support cancer cell survival, their overstimulation by PCAIs led to increased oxidative stress, damaging the cells and inducing cell death by apoptosis. The compound also reduced levels of RAC1 and CDC42, proteins involved in maintaining cell shape and movement. These alterations resulted in cytoskeletal disruption and reduced structural integrity, making the cancer cells more vulnerable and less capable of spreading. Importantly, the effects of NSL-YHJ-2-27 persisted after the compound was removed, suggesting long-term control over AI resistant cancer cells may be possible.“PCAIs inhibited cell proliferation and colony formation by 95% and 74%, respectively, increased active caspase 7 and BAX 1.5-fold and 56%, respectively. NSL-YHJ-2-27 (10 μM) induced LTLT-Ca spheroid degeneration by 61%.”As a new class of targeted molecules, PCAIs represent an innovative approach distinct from traditional endocrine therapies. Their ability to affect multiple cellular mechanisms simultaneously makes them promising candidates for future drug development.Overall, this study presents a promising new approach for treating AI therapy-resistant breast cancer. By targeting cellular pathways that support survival and mobility, PCAIs like NSL-YHJ-2-27 could provide a novel strategy to manage advanced or resistant forms of the disease. Further research, including in vivo studies and clinical trials, will be essential to confirm these findings and evaluate their therapeutic potential.DOI - https://doi.org/10.18632/oncotarget.28759Correspondence to - Nazarius S. Lamango - nazarius.lamango@famu.eduVideo short - https://www.youtube.com/watch?v=8xQEilloO9QSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28759Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, PCAIs, ROS, MAPK, PI3K/AKT, LTLT-Ca cellsTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
Lung cancer, particularly non-small cell lung cancer (NSCLC), is the deadliest cancer worldwide. Cigarette smoking is one of the main causes, but not every smoker develops the disease. This suggests that other biological factors help determine who develops cancer.Researchers from the Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indianapolis, and from the Richard L. Roudebush Veterans Affairs Medical Center have now found that cigarette smoke, combined with a weakened DNA repair system, can trigger the early stages of lung cancer, particularly NSCLC. This work, led by first author Nawar Al Nasralla and corresponding author Catherine R. Sears, was recently published in Volume 16 of Oncotarget.Full blog - https://www.oncotarget.org/2025/08/11/cigarette-smoke-and-weak-dna-repair-a-double-hit-behind-lung-cancer-risk/Paper DOI - https://doi.org/10.18632/oncotarget.28724Correspondence to - Catherine R. Sears - crufatto@iu.eduVideo short - https://www.youtube.com/watch?v=UEiCz834a8cSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28724Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, DNA repair, DNA damage, lung adenocarcinoma, squamous cell carcinoma, Xeroderma Pigmentosum Group C (XPC)To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY – August 11, 2025 – A new #researchpaper was #published in Volume 16 of Oncotarget on July 25, 2025, titled “Dissecting the functional differences and clinical features of R-spondin family members in metastatic prostate cancer.”In this study, researchers led by first author Aiden Deacon and corresponding author Justin Hwang from the University of Minnesota-Twin Cities investigated a group of genes known as the R-spondin family (RSPO1/2/3/4) in advanced prostate cancer (PC). The RSPO gene family regulates Wnt signaling, a pathway involved in cancer progression.Prostate cancer is the most common cancer among men in the United States and becomes especially dangerous when it spreads beyond the prostate. Most patients are treated with hormone therapies that target the androgen receptor; however, many tumors eventually become resistant.The research team analyzed thousands of tumor samples and found that RSPO2 alterations were more common than changes in other R-spondin genes or even some well-known cancer-related genes like CTNNB1 and APC. RSPO2 amplification occurred in over 20% of metastatic prostate cancer. Patients with these alterations showed signs of more aggressive disease, including higher mutation rates and greater tumor complexity.Using laboratory models, the team discovered that RSPO2 increases cancer cell growth and triggers a biological process called epithelial-mesenchymal transition (EMT). EMT is known to promote tumor spread and resistance to standard treatments. Unlike other genes in the same pathway, RSPO2 also appeared to reduce the activity of androgen receptor genes, suggesting it drives a type of prostate cancer that no longer relies on hormones for growth.“In cell lines, RSPO2 overexpression caused up-regulation of EMT pathways, including EMT-regulatory transcription factors ZEB1, ZEB2, and TWIST1.”Importantly, RSPO2 showed structural differences from other R-spondin proteins, which may allow researchers to design drugs that specifically block its activity. Current therapies targeting the Wnt pathway are limited, and there are no approved drugs that inhibit RSPO2. However, this study highlights RSPO2 as a promising therapeutic target, especially for patients who do not respond to existing hormone-based treatments.This research adds critical knowledge about how aggressive prostate cancers develop and persist despite therapy. The identification of RSPO2 as a key driver of disease progression opens new possibilities for treatment strategies aimed at improving outcomes for patients with advanced prostate cancer.DOI - https://doi.org/10.18632/oncotarget.28758Correspondence to - Justin Hwang - jhwang@umn.eduVideo short - https://www.youtube.com/watch?v=iyu5D_c1dbYSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28758Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, RSPO2, prostate cancer, Wnt signaling, genomics, therapeuticsTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
Prostate cancer is the second most diagnosed cancer among men worldwide and remains a leading cause of cancer-related death. While early forms of the disease can usually be treated successfully, advanced cases remain a major challenge. Scientists have now discovered a new potential way to slow the growth of advanced, treatment-resistant prostate cancer. These results were recently published in Volume 16 of Oncotarget by researchers from the University of Cincinnati College of Medicine.Understanding Advanced Prostate CancerEarly-stage prostate cancer can often be treated successfully. Most treatments work by lowering testosterone levels or blocking the hormone from activating the androgen receptor (AR), which drives cancer growth.In some patients, however, the disease progresses to castration-resistant prostate cancer (CRPC). Even with drastic reductions in testosterone levels, the tumors continue to grow at this stage. CRPC is much more difficult to treat, and current therapies such as hormone blockers or chemotherapy typically extend life by only a few months.One reason for this resistance is that cancer cells often switch to a different form of the androgen receptor called AR-V7. This variant remains permanently active, even without testosterone, making hormone-based drugs less effective. Because of this, new treatment strategies that work independently of hormone levels are needed.The Study: Targeting a New Weakness in Prostate Cancer CellsIn the study titled “Targeting PCNA/AR interaction inhibits AR-mediated signaling in castration resistant prostate cancer cells,” researchers Shan Lu and Zhongyun Dong from the University of Cincinnati College of Medicine investigated a new way to block CRPC growth.Full blog - https://www.oncotarget.org/2025/07/29/a-new-way-to-target-resistant-prostate-cancer-cells/Paper DOI - https://doi.org/10.18632/oncotarget.28722Correspondence to - Zhongyun Dong - dongzu@ucmail.uc.eduVideo short - https://www.youtube.com/watch?v=fiJWZ_fKxgsSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28722Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, PCNA, androgen receptor, PCNA inhibitors, AR splicing variants, CRPCTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - July 29, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on July 25, 2025, titled “Comprehensive genomic profiling of over 10,000 advanced solid tumors.”In this study, led by Jean-Paul De La O from Exact Sciences Corporation, researchers analyzed data from over 10,000 solid tumor samples from patients with advanced cancer and found that more than 90 percent contained genetic changes that could guide treatment. This work demonstrates the growing impact of large-scale tumor DNA and RNA testing on patient care.The researchers retrospectively analyzed OncoExTra assay information for 31 types of cancer, including breast, colorectal, prostate, lung, and ovarian cancers. Their analysis revealed that nearly a third of patients had alterations associated with approved drugs for their specific cancer, while another third had changes linked to therapies approved for other cancers. These results show that detailed genetic profiling could expand treatment choices.“Biomarkers associated with on- or off-label FDA-approved therapies were detected in 29.2% and 28.0% of samples, respectively.”Another relevant discovery was that many important mutations occurred at very low levels, which are often missed by simpler tests. By using a broad and highly sensitive approach, the scientists were able to identify these rare mutations. They also reported that 7.5 percent of samples carried gene fusions, unusual genetic events that can drive cancer growth. Such findings can be critical in selecting therapies that specifically target these abnormalities.The study also highlighted the value of RNA sequencing in detecting fusion events that traditional DNA tests might miss. Prostate cancer and certain sarcomas showed particularly high rates of these fusion alterations. This type of information can refine cancer diagnosis and improve therapy planning.In addition, the researchers identified changes in several major cancer-related pathways, including those that control cell growth, DNA repair, and immune system response. Alterations in these pathways can point to newer treatment options, such as immunotherapy or drugs designed to block specific cell signals.Overall, this study shows that comprehensive genomic profiling can guide more personalized cancer care by identifying mutations, gene fusions, and other molecular patterns. Advanced testing methods like the OncoExTra assay reveal treatment opportunities even in advanced cancers, ensuring that subtle but important genetic changes are detected.DOI - https://doi.org/10.18632/oncotarget.28757Correspondence to - Jean-Paul De La O - jdelao@exactsciences.comVideo short - https://www.youtube.com/watch?v=awiRhDfiMTESign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28757Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, solid tumors, comprehensive genomic profiling, matched therapy, gene fusions, limit of detectionTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY – July 24, 2025 – A new #casereport was #published in Volume 16 of Oncotarget on July 23, 2025, titled “Extracorporeal blood filtration leading to tumor growth arrest and reduced analgesic requirements in Stage IV poorly differentiated pancreatic adenocarcinoma: A case report.”In this report, Susanna Ulahannan from the University of Oklahoma Health Sciences Center and colleagues describe the use of extracorporeal blood filtration in a patient with metastatic pancreatic cancer. The patient experienced clinical improvement, reduced pain, and no signs of new tumor growth over 12 months of follow-up.Metastatic pancreatic cancer is difficult to treat and is often diagnosed at an advanced stage. In this case, a 51-year-old woman with stage IV poorly differentiated adenocarcinoma chose not to undergo standard chemotherapy. Instead, she received extracorporeal blood filtration with the Seraph® 100 device, which is designed to remove circulating tumor cells (CTCs) from the bloodstream. CTCs are thought to contribute to the spread of cancer to other organs.“Circulating tumor cells (CTC’s) are tumor cells that are shed from the primary tumor and travel via blood or lymphatic system to form micro metastases in distant organs under a suitable environment.“The patient received between nine and twelve treatments over the course of a year. These treatments were performed both abroad, where the device is approved for this use, and under a clinical protocol in the United States. Medical imaging showed that her disease remained stable, with no new metastases detected. She also reported improvements in appetite, energy levels, and pain control. Her opioid use was reduced by 90%.Blood samples confirmed a drop in CTC levels after treatment. This observation supports the idea that removing CTCs might help limit cancer progression in some patients. However, given that this is a single case report, larger clinical studies are needed to evaluate the effectiveness of this approach.The mechanism behind the patient’s pain relief is not fully understood. Authors suggest that it may be related to the reduction of tumor cells or inflammatory molecules in the blood. Researchers noted that pro-inflammatory cytokines, known to influence pain, could also have been affected by the filtration process.This is the first documented case of stable disease and reduced symptoms following CTC filtration in advanced pancreatic cancer. While these findings should not be generalized, they highlight an approach outside standard protocols that should be further explored in clinical research. Future studies will be needed to determine whether this method can contribute to symptom management or disease control in other patients with metastatic pancreatic cancer.DOI - https://doi.org/10.18632/oncotarget.28756Correspondence to - Susanna Ulahannan - susanna-ulahannan@ouhsc.eduVideo short - https://www.youtube.com/watch?v=dro6iUGDrVQSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28756Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, extracorporeal blood filtration, circulating tumor cells, metastatic pancreatic cancer, seraph 100, OncoBindTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY – July 22, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on July 21, 2025, titled “Statins exhibit anti-tumor potential by modulating Wnt/β-catenin signaling in colorectal cancer.”In this work, led by first author Sneha Tripathi from the Indian Institute of Science Education and Research and corresponding author Sanjeev Galande from the Center of Excellence in Epigenetics at Shiv Nadar University, researchers discovered that statins, widely used to lower cholesterol, may also suppress colorectal cancer growth. This finding highlights a potential new role for these common drugs in cancer prevention and therapy.Colorectal cancer is one of the leading causes of cancer-related deaths worldwide, and new strategies are urgently needed to improve treatment results. Statins, originally developed to lower cholesterol levels, have gained attention for their possible anti-cancer properties. The study investigated how statins affect the Wnt/β-catenin signaling pathway, a critical driver in colorectal cancer development and progression.The researchers discovered that statins disrupt the Wnt/β-catenin signaling pathway, leading to lower levels of tumor-promoting proteins and to cancer-suppressing cellular behaviors. Experiments in both colorectal cell cultures and mouse models confirmed that statins reduced tumor growth without causing noticeable side effects. This study further revealed that statins downregulate SATB1, a protein linked to aggressive tumor behavior, while increasing SATB2, a protein with tumor-suppressing effects. These changes made the cancer cells less able to grow and spread.“This reciprocal regulation shifts cellular phenotypes between epithelial and mesenchymal states in 3D spheroid models.”Overall, the findings suggest that statins could be repurposed to complement existing colorectal cancer treatments or even be used in preventive strategies for high-risk individuals. By targeting the molecular machinery that drives colorectal tumor development, statins offer a promising, accessible, and well-understood option for further research in cancer therapy.This research opens the door to larger clinical studies to explore how best to integrate statins into cancer care. If successful, this approach could provide a cost-effective strategy for reducing the global burden of colorectal cancer, which remains a significant health challenge.DOI - https://doi.org/10.18632/oncotarget.28755Correspondence to - Sanjeev Galande - sanjeev.galande@snu.edu.inVideo short - https://www.youtube.com/watch?v=A95ICULaH3YSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28755Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, colorectal cancer, statins, SATB1, Wnt/β-catenin signaling, tumor-suppressive phenotypeTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - July 18, 2025 – A new #editorial was #published in Volume 16 of Oncotarget on July 16, 2025, titled “microRNAs in soft tissue sarcoma: State of the art and barriers to translation.”In this article, Elizaveta K. Titerina, Alessandro La Ferlita, and Joal D. Beane from Ohio State University discuss the role of microRNAs in soft tissue sarcomas (STS), a rare and diverse group of cancers that begin in connective tissues, like bone or fat. The authors explain how these small molecules regulate cancer-related processes and highlight their potential as non-invasive biomarkers for diagnosis and monitoring. They also outline the main challenges that need to be addressed before microRNA-based strategies can be used in clinical settings.Soft tissue sarcomas include over 50 subtypes, making precise diagnosis and effective treatment difficult. The editorial describes how microRNAs influence cancer growth, spread, and response to therapies. Because microRNAs are stable in body fluids like blood and saliva, they could be used for early detection and to help guide treatment decisions. Such as, certain groups of microRNAs are linked to how patients respond to specific drugs, showing their potential as tools for precision medicine.“For example, miR-17-92 and miR-106b-25 clusters have been associated with sensitivity or resistance to eribulin in STS.”The authors also explain that microRNAs could help distinguish between tumor types that are often difficult to differentiate, such as benign lipomas and malignant liposarcomas. Recognizing these differences is crucial for guiding treatment decisions. Specific patterns of microRNA expression in blood samples may enable clinicians to make quicker and more reliable diagnoses without the need for invasive procedures. Beyond their diagnostic role, microRNAs are also being explored as therapeutic tools, but applying microRNA-based therapies to patients remains challenging. These molecules can act as either cancer promoters or suppressors, depending on the environment, which complicates the development of safe and targeted treatments. However, new delivery methods such as lipid nanoparticles show promise in improving precision and safety.Overall, microRNAs are emerging as an important focus in STS research, offering new possibilities for advancing diagnosis, prognosis, and treatment. As researchers continue to address the current challenges, these small molecules could become valuable tools in improving cancer care.DOI - https://doi.org/10.18632/oncotarget.28754Correspondence to - Joal D. Beane, joal.beane@osumc.eduVideo short - https://www.youtube.com/watch?v=MlLGA8BObPQSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28754Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, soft tissue sarcoma, liposarcoma, microRNA, small non-coding RNA, cancer biomarkersTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - July 16, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on July 9, 2025, titled “A novel anti-human CD25 mAb with preferential reactivity to activated T regulatory cells depletes them from the tumor microenvironment.”In this study, researchers from the National Institute of Allergy and Infectious Diseases, led by first author Maja Buszko and corresponding author Ethan M. Shevach, discovered a new monoclonal antibody that selectively targets a subset of immune cells called regulatory T cells (Tregs). These cells, while normally important for preventing autoimmunity, also can block the body’s ability to fight cancer by suppressing anti-tumor immune responses. This discovery could lead to novel cancer therapies that strengthen the immune system’s capacity to attack tumors.The researchers identified an anti-CD25 monoclonal antibody with several atypical properties and named it 2B010. To evaluate its effects, they used humanized mice, laboratory mice that are engineered to carry human immune cells, to closely mimic how human immune systems respond to cancer. The treatment of these mouse models with 2B010 significantly decreased the number of Tregs in tumors and boosted the activity of CD8+ T cells, which are essential for killing cancer cells. Importantly, 2B010 worked without disrupting other key immune functions. Unlike traditional Anti-CD25 antibodies, it did not interfere with interleukin-2 (IL-2) signaling, which is essential for the growth and activity of effector T cells that fight cancer. “2B010 also had no effect on IL-2 induced STAT5 phosphorylation or CD4+ T cell proliferation in vitro while both were blocked by Clone D1 further supporting the view that 2B010 does not recognize the IL-2 binding site.”This finding is especially significant because high levels of Tregs in tumors are associated with poor outcomes in many cancers. By specifically removing these cells, 2B010 may help overcome one of the main barriers to current immunotherapy approaches. Its ability to preserve IL-2 signaling could also make it safer and more effective when used alone or in combination with existing therapies such as immune checkpoint inhibitors.While the 2B010 antibody showed strong effects in reducing Tregs and boosting immune cell activity, the study did not observe changes in tumor size in these models. Researchers suggest this may be due to limitations in the preclinical systems used, such as the lack of tumor-specific T cells in humanized mice. Nevertheless, these findings demonstrate that 2B010 has a unique mechanism of action that could complement other cancer immunotherapies in future clinical trials.In conclusion, the development of 2B010 is a promising step toward selectively disrupting the immune suppressive environment in tumors. As researchers continue to refine and test this antibody, it could become a powerful tool for enhancing the effectiveness of cancer treatments and improving outcomes for patients.DOI - https://doi.org/10.18632/oncotarget.28752Correspondence to - Ethan M. Shevach - eshevach@Niaid.NIH.govVideo short - https://www.youtube.com/watch?v=2NJcGsI7WXASign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28752Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, Treg, CD25, TME, mAb, GVHDTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
Scientists have uncovered a promising new strategy to weaken cancer cells’ natural defense mechanisms, potentially making chemotherapy more effective. In a study published in Volume 16 of Oncotarget, researchers identified the protein PRDX1 as a key player in helping tumors resist treatment. By targeting this protein, they propose a novel way to combat aggressive, treatment-resistant cancers.Understanding Why Some Cancers Resist TreatmentChemotherapy works by damaging the DNA of cancer cells, forcing them to self-destruct. However, many cancers develop robust repair systems that fix this damage, allowing the tumor to survive and grow. A central component of this repair machinery is a protein called ATM, which acts like a first responder in the cell, detecting DNA damage and coordinating its repair.In ovarian cancer and other aggressive tumors, high levels of ATM have been associated with poor survival rates and resistance to chemotherapy.The Study: How PRDX1 Protects Cancer CellsThe study, titled “PRDX1 protects ATM from arsenite-induced proteotoxicity and maintains its stability during DNA damage signaling,” was led by first author Reem Ali and corresponding author Dindial Ramotar from Hamad Bin Khalifa University in Qatar, in collaboration with researchers from the University of Nottingham in the UK. Full blog - https://www.oncotarget.org/2025/07/14/prdx1-identified-as-key-to-chemotherapy-resistance-in-cancer-cells/Paper DOI - https://doi.org/10.18632/oncotarget.28720Correspondence to - Dindial Ramotar - dramotar@hbku.edu.qaVideo short - https://www.youtube.com/watch?v=suOhF7mPlNQSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28720Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, redox signaling, homologous recombination, protein interaction, cell cycle, protein modificationTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY – July 14, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on June 25, 2025, titled “Hypoxia induced lipid droplet accumulation promotes resistance to ferroptosis in prostate cancer.”In this study, researchers led by Shailender S. Chauhan and Noel A. Warfel from the University of Arizona discovered that prostate cancer cells survive treatment by storing fats in tiny cellular compartments when oxygen levels are low. This process makes the cancer cells less vulnerable to a type of cell death known as ferroptosis. The findings provide new insight into why prostate tumors often resist therapies and suggest potential strategies to improve treatment outcomes.This study focused on ferroptosis, a form of programmed cell death that relies on iron and lipid oxidation to destroy cancer cells. Researchers tested prostate cancer cells under normal and low oxygen conditions and found that hypoxia, or reduced oxygen levels, allowed cancer cells to build up lipid droplets (LD). These structures act as storage units for fats, shielding cancer cells from oxidative damage and preventing ferroptosis from occurring.The researchers found that this adaptation of prostate cancer cells made them less sensitive to ferroptosis-inducing drugs like Erastin and RSL3, even when these drugs were combined for a stronger effect. The team also reported that hypoxia caused significant changes in lipid metabolism, decreasing the availability of specific fatty acids that normally promote ferroptosis. “Transcriptomic analysis revealed that hypoxia significantly reduced the expression of genes related to incorporating polyunsaturated fatty acids into phospholipids (ACSL4, LPCAT3), and parallel lipidomic analysis demonstrated that hypoxia significantly decreased the levels of the ferroptosis-prone lipid class, phosphatidylethanolamine (PE) and increased production of neutral lipid species, cholesteryl ester (ChE (22:5)) and triglycerides (TG(48:1), TG:(50:4), and TG(58:4)).”This research highlights the importance of the tumor microenvironment, particularly oxygen levels, in shaping how cancer cells respond to therapy. By altering their metabolism and storing lipids, prostate tumors may evade treatments designed to trigger ferroptosis. These findings underscore the need to develop new strategies targeting LD dynamics or lipid metabolism to overcome this resistance.Understanding how prostate cancer (Pca) adapts to survive in hypoxic conditions offers a potential avenue for improving therapies. For example, preventing lipid accumulation in cancer cells or releasing stored fats may restore their sensitivity to ferroptosis and improve the effectiveness of current therapies. This approach could have broader implications for treating other solid tumors that share similar metabolic features.DOI - https://doi.org/10.18632/oncotarget.28750Correspondence to - Noel A. Warfel - warfelna@arizona.edu, and Shailender S. Chauhan - shailenderc@arizona.eduVideo short - https://www.youtube.com/watch?v=xFypDT4ALmcSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28750Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, hypoxia, lipid droplets, ferroptosis, resistance, prostateTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY – July 9, 2025 – A new #review was #published in Volume 16 of Oncotarget on June 25, 2025, titled “Challenges and resistance mechanisms to EGFR targeted therapies in head and neck cancers and breast cancer: Insights into RTK dependent and independent mechanisms.”Researchers from the University of Cincinnati and Cincinnati Veterans Affairs Medical Center reviewed current research on why Epidermal Growth Factor Receptor (EGFR)-targeted therapies often fail in breast and head and neck cancers. The article by Shreya Shyamsunder, Zhixin Lu, Vinita Takiar, and Susan E. Waltz explores how cancer cells evade these treatments by activating alternative survival pathways. This review offers an in-depth look at the molecular barriers to EGFR inhibition and provides insights that could inform the development of more effective and durable treatments.EGFR is a critical protein that regulates cell growth and survival, and it is frequently overexpressed in breast and head and neck cancers. Although therapies targeting EGFR showed early promise, resistance has become a significant challenge. In breast cancer, resistance mechanisms include the movement of EGFR from the cell surface into the nucleus, where it promotes DNA repair, as well as ligand-dependent activation that helps tumor growth despite therapy. In head and neck cancers, resistance often arises from inflammatory signaling through the TLR4-MyD88 pathway and the loss of tumor suppressor genes like PTEN, which allow cancer cells to bypass EGFR inhibition. The review also describes how tumor cells in both cancers commonly activate other receptor tyrosine kinases (RTKs), such as MET, AXL, and RON, to continue growing even when EGFR is blocked.By analyzing these resistance mechanisms, the authors highlight combination therapies from current research that target EGFR and other key molecular pathways. Strategies such as dual inhibition of EGFR and MET or blocking inflammation-driven survival signals may enhance treatment outcomes. Several clinical trials are evaluating these approaches in patients. For example, in breast cancer, combinations of EGFR inhibitors with chemotherapy and immune checkpoint inhibitors are being tested to improve responses, particularly in triple-negative breast cancer. In head and neck cancers, trials are investigating EGFR-blocking antibodies like cetuximab combined with immunotherapies such as pembrolizumab and nivolumab. These efforts aim to overcome resistance and provide more effective treatment options for patients with EGFR-driven tumors. The review also emphasizes the necessity of identifying biomarkers to predict which patients are most likely to benefit from EGFR-based therapies.“A recent phase 1 study has shown that patients with recurrent or metastatic head and neck cancer who received BCA101, a bifunctional dual targeting drug that targets EGFR and TGF-β in combination with pembrolizumab, were able to achieve an overall response rate of 65%.”This work brings together current knowledge about EGFR resistance and illustrates the difficulties involved in treating breast and head and neck cancers. By mapping the many ways tumors overcome EGFR inhibition, the review highlights opportunities for more tailored and effective treatments in the future.DOI - https://doi.org/10.18632/oncotarget.28747Correspondence to - Susan E. Waltz - susan.waltz@uc.edu, and Vinita Takiar - takiarva@ucmail.uc.eduVideo short - https://www.youtube.com/watch?v=RD2W-F3_aX4About Oncotarget:Website - https://www.oncotarget.comFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - July 7, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on June 17, 2025, titled “Genetic characteristics of blastic plasmacytoid dendritic cell neoplasm: A single institution experience.”In this study, a research team led by first author Fei Fei and corresponding author Michelle Afkhami from the City of Hope Comprehensive Cancer Center investigated a rare and aggressive type of blood cancer called blastic plasmacytoid dendritic cell neoplasm (BPDCN). Their research uncovered frequent mutations in key genes and identified CCDC50 as a potential biomarker for diagnosis and disease monitoring. These findings could help improve how this cancer is detected and treated in the future.BPDCN most often affects older adults and is known for its rapid progression and poor survival rates. The researchers performed genetic sequencing on 21 patients to better understand the disease. They found that two genes, TET2 and ASXL1, were frequently mutated in these patients and were linked to worse survival, especially in those over 65 years old.“Our study revealed that TET2 (57%) and ASXL1 (33%) were the most frequently mutated genes, followed by NRAS (29%), SRSF2 (14%), ZRSR2 (14%), and KMT2D (14%).”The study also discovered that a gene called CCDC50 was expressed at much higher levels in BPDCN samples compared to other blood cancers, such as acute myeloid leukemia and chronic monomyelocytic leukemia. This suggests that CCDC50 may help clinicians distinguish BPDCN from other similar diseases. Importantly, CCDC50 levels dropped significantly in patients whose disease went into remission, highlighting its potential as a tool for tracking disease activity over time.Researchers further observed that patients who received stem cell transplants lived longer than those who did not, reinforcing the importance of this treatment approach. However, BPDCN remains a challenging disease with an overall poor outlook, making these findings an important step toward better care.This research provides new insights into the genetic changes behind BPDCN and points to CCDC50 as a promising marker to improve diagnosis and monitor treatment success. Larger studies will be needed to confirm these results and bring these discoveries closer to use in routine medical practice.DOI - https://doi.org/10.18632/oncotarget.28742Correspondence to - Michelle Afkhami - mafkhami@coh.orgVideo short - https://www.youtube.com/watch?v=wUjr3uU3onISign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28742Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Next-generation sequencing (NGS), CCDC50To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
Liver cancer, especially hepatocellular carcinoma (HCC), remains a major health concern worldwide. In Latin America, the situation becomes more difficult due to limited access to advanced treatments and the high prevalence of underlying liver diseases. A recent research paper, published in Volume 16 of Oncotarget by researchers from Argentina, Brazil, Chile, and Colombia, offers valuable insights into how patients in the region respond to a widely used immunotherapy regimen. This real-world study explores both the effectiveness of treatment and the risks of immune-related side effects.Understanding Hepatocellular Carcinoma: Why It is So Difficult to TreatHepatocellular carcinoma is often diagnosed at an advanced stage and frequently occurs in people with pre-existing liver conditions such as cirrhosis. Standard treatments like surgery or local therapies are not always possible in these cases. In recent years, the combination of two drugs—atezolizumab and bevacizumab—has shown promise in extending survival. However, most of the evidence comes from controlled clinical trials that may not represent the realities faced by healthcare providers and patients in Latin America.The Study: Immunotherapy for Hepatocellular Carcinoma in Latin AmericaIn a multicenter study titled “Immune-mediated adverse events following atezolizumab and bevacizumab in a multinational Latin American cohort of unresectable hepatocellular carcinoma,” led by Leonardo Gomes da Fonseca from Hospital das Clínicas, Universidade de São Paulo, Brazil, and Federico Piñero from Hospital Universitario Austral, Argentina, researchers aimed to fill that gap. The study included 99 patients with advanced HCC from Argentina, Brazil, Chile, and Colombia. All patients received the combination of atezolizumab and bevacizumab. The main objectives were to assess how frequently immune-related side effects, known as immune-related adverse events (irAEs), occurred and whether these events affected overall survival.Full blog - https://www.oncotarget.org/2025/07/02/immunotherapy-safety-for-hepatocellular-carcinoma-in-latin-america-insights-from-a-real-world-study/Paper DOI - https://doi.org/10.18632/oncotarget.28721Correspondence to - Federico Piñero - fpinerof@cas.austral.edu.arVideo short - https://www.youtube.com/watch?v=gk3oQwzIC-ESign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28721Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, liver cancer, immunotherapy, adverse events, immunology, real-world To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY – July 1, 2025 – A new #review was #published in Volume 16 of Oncotarget on June 17, 2025, titled “Optimizing enfortumab vedotin plus pembrolizumab therapy.”First authors Elias Antoine Karam of the Gustave Roussy and Saint-Joseph University of Beirut and Yaghi César Céline from the Saint-Joseph University of Beirut, along with their colleagues, reviewed recent developments about treating advanced urothelial carcinoma (aUC), an aggressive form of bladder cancer. Their review highlights how combining enfortumab vedotin and pembrolizumab as a first-line treatment offers a major improvement for patients with limited options and poor prognoses.Advanced urothelial cancer has traditionally been treated with platinum-based chemotherapy, which often causes serious side effects and offers limited long-term benefit. Many patients are even ineligible for it due to underlying health conditions. The new combination presents a more effective and better-tolerated alternative, as shown in recent clinical trials reviewed by the authors.Enfortumab vedotin targets Nectin-4, a protein present in most urothelial cancer cells, delivering a cancer-killing agent directly into tumors. Pembrolizumab helps the immune system detect and destroy cancer cells. Together, they have shown strong results in extending survival with fewer serious side effects than chemotherapy. These findings led to FDA approval in 2023 for use in a broad range of patients, including those unable to tolerate traditional treatments.“In the phase II KEYNOTE-052 study, pembrolizumab demonstrated significant efficacy as initial therapy in patients with aUC who were ineligible for a cisplatin-based regimen.”The review also compares this new approach with other evolving strategies, such as therapies using nivolumab and chemotherapy combinations. Among current first-line options, enfortumab vedotin and pembrolizumab have produced the most promising outcomes. However, the best course of action following disease progression remains unclear.Other important challenges raised in the review include the high cost of the new therapies, limited patient access to them, and the absence of reliable biomarkers to predict individual response. The authors call for further studies to refine treatment strategies and explore blood-based tools that could guide therapy decisions and minimize side effects.This review offers a clear summary of how recent clinical advances are reshaping the treatment of aUC. It reflects a shift away from traditional chemotherapy toward immunotherapy and targeted, personalized treatments that aim to extend survival and improve quality of life.DOI - https://doi.org/10.18632/oncotarget.28741Correspondence to - Elias Antoine Karam - eliaskaram18@gmail.comVideo short - https://www.youtube.com/watch?v=VrTXaF2qW2kSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28741Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, advanced urothelial carcinoma (aUC), enfortumab vedotin, pembrolizumab, treatment strategies, bladder cancerTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY – June 27, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on June 17, 2025, titled “Molecular landscape of HER2-mutated non-small cell lung cancer in Northeastern Brazil: Clinical, histopathological, and genomic insights.”In this study, researchers led by first authors Cleto Dantas Nogueira from the Federal University of Ceará and Argos Pathology Laboratory and Samuel Frota from Argos Pathology Laboratory, along with corresponding author Fabio Tavora from the previously mentioned institutions and Messejana Heart and Lung Hospital, investigated how HER2 gene mutations appear in cases of non-small cell lung cancer (NSCLC) in Northeastern Brazil. The team found that HER2 mutations showed significant genetic diversity and were often associated with other cancer-related genetic changes. These findings revealed diagnostic and treatment challenges in a population that is rarely studied, emphasizing the need for expanded access to molecular testing and targeted therapies.HER2 mutations are a known factor in several cancers, including breast and gastric cancers. In lung cancer—particularly NSCLC—these mutations are less common but remain clinically significant. Most existing research on HER2-mutated lung cancer focuses on high-income countries, leaving important gaps in knowledge about underrepresented regions such as Latin America. This study helps fill that gap by analyzing 13 patients with HER2-mutated NSCLC using clinical, pathological, and genomic data.The patients ranged in age from 34 to 82 years, and more than half were women. About half had never smoked. Their tumors often displayed complex genetic profiles, including additional mutations in genes such as TP53, KRAS, and STK11. The most common HER2 mutation identified was an insertion in exon 20, a known hotspot for activating mutations.“Trastuzumab deruxtecan (T-DXd) is the first HER2-targeted agent to show clinical efficacy in HER2-mutant non-small cell lung cancer (HER2m NSCLC).”Treatment strategies among the patients varied. Only one individual received HER2-targeted therapy. Most were treated with surgery, chemotherapy, immunotherapy, or a combination of these approaches. Outcomes also differed, with some patients surviving for years and others dying within months of diagnosis. These findings reinforce the need for early diagnosis and improved access to advanced treatments, particularly in low-resource settings.The study emphasizes the value of comprehensive molecular profiling in NSCLC. Because HER2 mutations often occur alongside other genetic alterations, full genomic analysis is crucial for guiding treatment decisions. Yet, such testing is not always available. The researchers propose a tiered diagnostic approach, beginning with basic screening and expanding to more advanced tests when necessary, to enhance patient care.This study provides valuable insights into the molecular characteristics of HER2-mutated NSCLC in a Brazilian population, highlighting the complexity and clinical relevance of these alterations. Larger studies are needed to clarify the prevalence and prognostic significance of HER2 mutations, as well as their impact on treatment response and survival. This knowledge is essential for advancing effective HER2-targeted therapies. The findings also support broader implementation of international clinical guidelines in Latin America and highlight the critical need to include underrepresented populations in cancer research.DOI - https://doi.org/10.18632/oncotarget.28737Correspondence to - Fabio Tavora - stellacpak@outlook.comVideo short - https://www.youtube.com/watch?v=hr5R9iDBFFITo learn more about Oncotarget, please visit https://www.oncotarget.com.MEDIA@IMPACTJOURNALS.COM
BUFFALO, NY – June 24, 2025 – A new precision #oncology paper was #published in Volume 16 of Oncotarget on June 17, 2025, titled “Case Report WIN-MTB-2023001 WIN International Molecular Tumor Board A 62-year-old male with metastatic colorectal cancer with 5 prior lines of treatment.”In this report, led by Alberto Hernando-Calvo from Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology; Razelle Kurzrock from WIN Consortium and Medical College of Wisconsin; Oncotarget Editor-in-Chief Wafik S. El-Deiry from WIN Consortium and Legorreta Cancer Center at Brown University; and corresponding author Shai Magidi, also from WIN Consortium, along with colleagues, describe the case of a 62-year-old man with metastatic colorectal cancer who underwent multiple lines of therapy. After analysis, the WIN International Molecular Tumor Board proposed different personalized treatment plans based on the tumor’s unique genetic mutations. This case highlights the growing role of precision oncology in guiding therapies for patients with treatment-resistant cancers.Colorectal cancer is one of the deadliest cancers worldwide, and managing advanced cases remains a significant challenge. This patient had already received five prior treatment regimens, including chemotherapy and targeted therapies. Although some treatments were initially beneficial, the cancer eventually developed resistance. Molecular analysis revealed key mutations in genes such as BRAF, MET, APC, TP53, and NRAS, which are often linked to aggressive tumor behavior and reduced treatment effectiveness.With limited standard options left, the patient’s case was presented and reviewed by the WIN International Molecular Tumor Board, a global panel of cancer experts. The team analyzed the clinical history and genetic profile to design new treatment approaches. These involved off-label drug combinations tailored to the specific mutations found in the tumor. For example, one approach combined trametinib, a drug that blocks cancer cell growth signals, with amivantamab, an antibody that attacks cancer-related proteins MET and EGFR, and regorafenib, which helps cut off blood supply to tumors and may counteract effects from APC and TP53 mutations.“Another option was trametinib at 1 mg daily, cetuximab (EGFR antibody), 250 mg/m² IV every two-weeks, and cabozantinib (MET and VEGFR inhibitor), 40 mg po daily.”This case reflects a shift in cancer care from standardized protocols to precision approaches, where therapy is selected based on a tumor’s molecular features. Such strategies aim to delay resistance and slow disease progression more effectively. The WIN International Molecular Tumor Board also discussed practical challenges, including access to medications, combining off-label drugs, and the difficulties of enrolling patients in clinical trials after multiple prior treatments.Although the ultimate treatment decision remained with the patient’s physician, this report shows how international collaboration and precision oncology can expand options for patients facing limited alternatives. It also emphasizes the value of repeat genetic analysis during disease progression to monitor new mutations in the tumor that may impact treatment.While the patient ultimately died from cancer progression, this case serves as a model for how molecular analysis and expert input can be used to guide treatment even in complex and metastatic colorectal cancer. As personalized cancer strategies continue to evolve, they may offer potential pathways for patients who have exhausted standard treatment options.DOI - https://doi.org/10.18632/oncotarget.28744Correspondence to - Shai Magidi - shai.magidi@winconsortium.orgVideo short - https://www.youtube.com/watch?v=uWDtWNgpK7ATo learn more about Oncotarget, please visit https://www.oncotarget.com.MEDIA@IMPACTJOURNALS.COM
BUFFALO, NY – June 20, 2025 – A new #review was #published in Volume 16 of Oncotarget on June 10, 2025, titled “Beyond DNA damage response: Immunomodulatory attributes of CHEK2 in solid tumors.”In this paper, led by first author Helen Qian and corresponding author Crismita Dmello from Northwestern University Feinberg School of Medicine, researchers compiled growing evidence that the CHEK2 gene, long known for its role in repairing DNA damage, may also influence how tumors respond to immunotherapy. Their analysis suggests that problems in CHEK2 function might make cancer cells more vulnerable to immune system attacks, highlighting a new opportunity to improve treatment outcomes in solid tumors.Immune checkpoint inhibitors (ICIs) have transformed cancer treatment; however, they are effective in only a subset of patients. This review suggests that tumors with reduced CHEK2 activity may accumulate more mutations that produce signals the immune system can recognize. These signals, known as neoantigens, help immune cells identify and destroy cancer cells more effectively. The review connects this process not only to CHEK2’s established role in the DNA damage response but also to a newly proposed function in shaping the immune environment of tumors.CHEK2 normally helps maintain genomic stability by enabling precise DNA repair. When this function is lost, cells rely on more error-prone repair methods, leading to additional mutations. These mutations can increase tumor mutational burden, which has been linked to better outcomes with immunotherapy. Beyond DNA repair, the review highlights a second mechanism: activation of the cGAS-STING pathway. This pathway detects fragments of damaged DNA and triggers inflammation that attracts immune cells to the tumor.The authors highlight studies where CHEK2-deficient tumors responded better to PD-1 inhibitors, a common type of immune checkpoint inhibitor. In both lab models and early-stage clinical settings, CHEK2 loss was associated with increased infiltration of CD8+ T cells—immune cells essential for attacking cancer cells. In cancers such as glioblastoma and renal cell carcinoma, which are typically resistant to immunotherapy, reduced CHEK2 expression was linked with more favorable immune activity and higher expression of interferon-related genes.The compiled evidence points to CHEK2 as a potential biomarker for identifying patients likely to respond to immunotherapy. In addition, combining CHEK2 inhibitors with existing immunotherapies may enhance anti-tumor effects, particularly in cancers with limited treatment options. The review notes that some clinical trials using the CHEK1/2 inhibitor prexasertib alongside immune checkpoint therapies have already shown promising early results.“The initial results from this Phase I clinical trial support the immunomodulatory role of CHEK2 expression and even suggest CHEK2 potentiates immunosuppression.”Although more research is needed to confirm these mechanisms and improve treatment approaches, this review underscores the expanding role of DNA repair genes like CHEK2—not only in maintaining genome integrity but also in helping the immune system fight cancer.DOI - https://doi.org/10.18632/oncotarget.28740Correspondence to - Crismita Dmello - stellacpak@outlook.comVideo short - https://www.youtube.com/watch?v=C26pEBc0itkSubscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - June 17, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on June 10, 2025, titled “Exceptional responders to immunotherapy in pancreatic cancer: A multi-institutional case series of a rare occurrence.”The study, led by first author Kavin Sugumar and corresponding author Jordan M. Winter, from University Hospitals Seidman Cancer Center, reports on a rare group of pancreatic cancer (PC) patients who responded remarkably well to immunotherapy, a treatment typically considered ineffective for this cancer type. The analysis, which includes data from 14 patients across multiple U.S. institutions, identifies outcomes that could help refine treatment strategies for one of the most aggressive and deadly forms of cancer.“Between 2020–21, 471 oncologists from 91 major cancer centers in the United States were contacted.”Pancreatic cancer has among the lowest survival rates and few effective therapies. While immunotherapy has transformed the treatment landscape for several other cancers, it generally offers little benefit for pancreatic cancer. However, this study highlights a small but important group of patients who experienced significant and sustained responses to immune-based treatment without chemotherapy. Most had advanced or metastatic disease and had already progressed after standard treatments.Among the 14 patients, 82% had partial tumor shrinkage, and nearly one-third had a notable decrease in tumor markers. The median progression-free survival was 12 months, and most patients were still alive at follow-up, with survival rates of 80% at one year and 70% at two years. These outcomes contrast sharply with standard therapies, which often provide only a few months of benefit for similar patients.Interestingly, while some patients had high microsatellite instability (MSI-high)—a known marker for immunotherapy success—more than half did not, suggesting other biological mechanisms may be involved. This result highlights the need for new biomarkers to be discovered to predict treatment response in future studies.This case series is the largest focused exclusively on exceptional immunotherapy responders in pancreatic cancer. By excluding patients who received chemotherapy, the study isolates the effects of immune-based drugs, including PD-1 inhibitors such as pembrolizumab and nivolumab, CTLA-4 inhibitors like ipilimumab, and agents targeting macrophages.While the sample size is small, the findings challenge the assumption that immunotherapy is ineffective for nearly all pancreatic cancer patients. The study suggests that, under certain biological conditions, this treatment can be remarkably successful. Further research is needed to understand the underlying mechanisms.This work supports the need to reconsider how clinical trials are designed for pancreatic cancer and who is eligible for immunotherapy. Broader criteria and more personalized molecular profiling could help uncover hidden opportunities for treatment in this highly lethal cancer.DOI - https://doi.org/10.18632/oncotarget.28739Correspondence to - Jordan M. Winter - jordan.winter@UHHospitals.orgVideo short - https://www.youtube.com/watch?v=VeWTcuVmqgMSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28739Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
Bladder cancer remains a significant clinical concern, with more than 85,000 new diagnoses and nearly 19,000 deaths reported annually in the United States. While current treatments like surgery, chemotherapy, and radiation can be effective for early-stage disease, many patients with advanced or recurrent cancer face limited options.A recent review, published in Oncotarget by researchers from the University of California, Irvine, analyzes the growing body of evidence supporting the combination of radiation therapy and immunotherapy for bladder cancer. Led by Nazmul Hasan, the work synthesizes clinical data and biological mechanisms that suggest this strategy could enhance anti-tumor responses in specific patient groups.Full blog - https://www.oncotarget.org/2025/06/16/exploring-a-combined-approach-radiation-and-immunotherapy-in-bladder-cancer/Paper DOI - https://doi.org/10.18632/oncotarget.28723Correspondence to - Nazmul Hasan - nhasan1@hs.uci.eduVideo short - https://www.youtube.com/watch?v=AxrZhIUXrOQSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28723Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - June 13, 2025 – A new #review was #published in Volume 16 of Oncotarget on June 4, 2025, titled “Applying the unattainable triangle in cardio-oncology care: Balancing cost, quality, and time.”In this review, first author John Hoverson, corresponding author Stella Pak, and colleagues from the University of Texas Health Science Center at San Antonio explore how the “unattainable triangle”—a business concept describing the trade-offs between cost, quality, and time—can help improve healthcare delivery in cardio-oncology. As cancer treatments become more complex and often affect the heart, this model highlights the challenge of providing care that is fast, effective, and affordable.Cardio-oncology is an emerging field focused on preventing and managing heart problems caused by cancer therapies. The review explains that high-quality cancer care often requires advanced diagnostics and close collaboration between oncologists and cardiologists, which can drive up costs and time demands. Understanding how to balance these pressures is essential for delivering better outcomes for patients.Many cancer survivors face long-term cardiovascular complications due to their treatment. Early monitoring and intervention can reduce these risks. However, these improvements often come with financial burdens, especially when key tests are not covered by insurance. Meanwhile, both patients and clinicians must manage the burden of tight appointment schedules, long clinic visits, and increasing demands on their time.To improve care quality, the authors emphasize the need for interdisciplinary teamwork and ongoing education. Surveys show that many clinicians are still unfamiliar with cardio-oncology guidelines, which can compromise care. The review also highlights the potential for artificial intelligence and digital tools to streamline care delivery, reduce wait times, and support both patients and providers.Importantly, the authors point out that improving one area—such as quality—can come at the expense of others, like cost or time. They encourage healthcare systems to take a balanced approach, setting clear goals and using integrated care models that consider all three elements of the triangle together.“While a perfect model for managing the unattainable triangle may be simply that, ‘unattainable’, investments in research, patient-centered care, data-driven decision-making, and financial alignment with payers will be crucial to the long-term success of both patient outcomes and the organization’s profitability.”While achieving perfect balance may be difficult, the review suggests that using the unattainable triangle as a guiding framework can help hospitals and clinicians make smarter, more sustainable decisions. As cardio-oncology continues to expand in response to the growing number of cancer survivors with cardiovascular needs, this approach could help improve patient outcomes and strengthen healthcare systems.DOI - https://doi.org/10.18632/oncotarget.28738Correspondence to - Stella Pak - stellacpak@outlook.comVideo short - https://www.youtube.com/watch?v=65-5eUuVyykSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28738Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, cardio-oncology, quality improvement, cardiology, oncologyTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - June 11, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on May 29, 2025, titled “Durable complete response in leptomeningeal disease of EGFR mutated non-small cell lung cancer to amivantamab, an EGFR-MET receptor bispecific antibody, after progressing on osimertinib.”A team led by first author Jinah Kim, from the University of Vermont Medical Center, and corresponding author Young Kwang Chae, from the Feinberg School of Medicine, reports a clinical case in which a patient with advanced non-small cell lung cancer (NSCLC) carrying rare EGFR mutations responded remarkably to amivantamab after other treatments had failed. The patient experienced a complete resolution of brain and spinal fluid metastases, suggesting that amivantamab may be a viable option for patients with uncommon genetic profiles and limited therapy options.Lung cancer remains one of the leading causes of cancer-related deaths worldwide. Patients with NSCLC who have rare mutations in the EGFR gene often face limited treatment options and poor outcomes, especially when the disease spreads to the brain or spinal fluid. This case involved a 67-year-old man diagnosed with NSCLC who had two rare EGFR mutations—G719A and A289V. After disease progression on osimertinib and other therapies, the patient began amivantamab monotherapy.Within six weeks, his lung tumor shrank by over 30 percent. By six months, imaging confirmed the disappearance of brain metastases and leptomeningeal disease, a serious condition affecting the membranes of the brain and spinal cord. Blood tests showed no detectable cancer-related mutations, and the patient, previously wheelchair-bound, regained the ability to walk and perform daily activities. This response has been sustained for more than 19 months. “Treatment produced a durable response over 19 months, including a 32.2% reduction in tumor size at six weeks, and complete resolution of brain metastases and LMD by six months.”Amivantamab is a bispecific antibody that targets EGFR and MET, two key drivers of tumor growth. While it is approved in combination regimens for common EGFR mutations, its effectiveness as a single agent in rare mutations or in treating brain metastases remains largely unproven. This case challenges the assumption that large antibody drugs cannot cross the blood-brain barrier and suggests that amivantamab may have potential in managing central nervous system involvement. Further research is needed to clarify how the drug achieves these effects and to explore its broader use in patients with rare EGFR mutations and limited treatment options.This case highlights three key findings: amivantamab may be effective against rare EGFR mutations, can be used as monotherapy, and may overcome the challenges of the blood-brain barrier. Although based on a single patient, the results provide encouraging evidence to support further investigation of amivantamab in treating difficult-to-manage forms of NSCLC.DOI - https://doi.org/10.18632/oncotarget.28730Correspondence to - Young Kwang Chae - young.chae@northwestern.eduVideo short - https://www.youtube.com/watch?v=RJX3rmtH7h8Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, amivantamab, monotherapy, rare EGFR mutation, NSCLC, leptomeningeal diseaseTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY — June 10, 2025 — The Ride for Roswell, one of the USA’s largest cycling events supporting cancer research, returns to Buffalo on Saturday, June 28, 2025. Hosted annually by Roswell Park Comprehensive Cancer Center, this community-wide event brings together riders, volunteers, and supporters to raise funds for cancer research, celebrate survivors, and honor those lost to the disease. Among the returning participants is the Open Access Team, led by team captain Sergei Kurenov. This year, the team is once again proudly sponsored by Impact Journals, the publisher of open access journals Oncotarget, Aging, Genes & Cancer, and Oncoscience.“For the last 10 years, I have continuously participated in the Ride for Roswell in honor of those who have bravely fought cancer,” said Kurenov. “This journey is deeply personal for me. My father battled cancer, and some of my closest friends have fought through prostate and lung cancer with incredible strength.”This year, the Open Access Team rides in honor of Dr. Mikhail (Misha) Blagosklonny, a visionary scientist who dedicated his career to advancing cancer and aging research. As the founding Editor-in-Chief of Oncotarget, Aging, and Oncoscience, Dr. Blagosklonny was a pioneer of open-access publishing. His groundbreaking work on mTOR signaling and rapamycin transformed our understanding of cancer biology and healthy lifespan extension.The 2025 Ride for Roswell features nine route options, ranging from 4 to 100 miles, all beginning at the University at Buffalo North Campus. Riders from across the USA and beyond are invited to participate and make a meaningful impact in the fight against cancer.This ride is more than just a journey on two wheels—it’s a commitment to building a future where no one has to fear a cancer diagnosis. There is still time to support the Open Open Access Team in the 2025 Ride for Roswell. Whether by donating, joining the team, or sharing their story, every action brings us closer to better treatments, deeper understanding, and, ultimately, a cure.Visit the Open Access Team page - https://give.roswellpark.org/site/TR/SpecialEvents/General?team_id=23320&pg=team&fr_id=2020About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY – June 9, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on May 20, 2025, titled “Cigarette smoke and decreased DNA repair by Xeroderma Pigmentosum Group C use a double hit mechanism for epithelial cell lung carcinogenesis.”In this study, led by first author Nawar Al Nasralla and corresponding author Catherine R. Sears, from the Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indianapolis and the Richard L. Roudebush Veterans Affairs Medical Center, researchers investigated how cigarette smoke and reduced DNA repair capacity contribute together to the development of lung cancer. They found that when a critical DNA repair protein called XPC is decreased and lung cells are exposed to cigarette smoke, the combination causes extensive damage and significantly increases cancer risk.Non-small cell lung cancer (NSCLC) develops through both genetic and environmental factors. This study focused on how cigarette smoke affects the body’s natural ability to repair DNA. The researchers studied the role of XPC, a protein essential for recognizing and repairing harmful DNA changes caused by tobacco smoke. They found that low levels of XPC — commonly seen in lung cancer patients — made lung cells less capable of repairing DNA. This made the cells unstable and more likely to become cancerous. These changes were most pronounced in normal lung cells, suggesting that the earliest stages of disease occur before cancer is even detected.The findings support a “double hit” model, where both cigarette smoke and reduced DNA repair work together to drive cancer development. In laboratory experiments, normal lung cells with low XPC levels showed more damage and cell death after cigarette smoke exposure. By contrast, lung cancer cells were more resistant to smoke damage, even when XPC was low, indicating that critical changes had likely occurred earlier in the disease process.“Our study suggests that cigarette smoke exposure leads to decreased XPC mRNA expression, exacerbates total and oxidative DNA damage, hinders NER, and may contribute to lung cancer development.”The study also showed that DNA repair ability declined significantly in healthy cells after smoke exposure, but this effect was not seen in cancer cells. In addition, the researchers confirmed that XPC gene activity was lower in actual lung tumor tissue compared to nearby healthy lung tissue. This pattern was consistent across both adenocarcinoma and squamous cell carcinoma, the two main types of NSCLC.These results add to our understanding of how lung cancer begins at the molecular level. By showing how cigarette smoke and reduced DNA repair combine to create genetic instability, the research points toward new strategies for prevention. A better understanding of XPC’s role could help identify high-risk individuals and inform future efforts to stop lung cancer before it begins.DOI - https://doi.org/10.18632/oncotarget.28724Correspondence to - Catherine R. Sears - crufatto@iu.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28724Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, DNA repair, DNA damage, lung adenocarcinoma, squamous cell carcinoma, Xeroderma Pigmentosum Group C (XPC)To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
Researchers at Brown University have developed a combination treatment that significantly increases survival in mice with glioblastoma (GBM), a highly aggressive and treatment-resistant brain cancer. The approach uses a new class of drugs called imipridones along with radiation therapy and standard chemotherapy. This triple therapy, known as IRT, was recently detailed in a study published in Oncotarget.Understanding Glioblastoma and the Need for Better TherapiesGlioblastoma is the most common and aggressive malignant brain tumor in adults. It grows quickly and is difficult to treat, often leading to poor outcomes. Most patients survive less than 15 months after diagnosis, even when treated with surgery, radiation, and the chemotherapy drug temozolomide (TMZ). This treatment may slow the disease, but it does not typically stop it.Full blog - https://www.oncotarget.org/2025/06/04/experimental-triple-therapy-improves-survival-in-glioblastoma-mouse-model/Paper DOI - https://doi.org/10.18632/oncotarget.28707Correspondence to - Wafik S. El-Deiry - wafik@brown.eduVideo short - https://www.youtube.com/watch?v=Q_mXy8mana0Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28707Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, glioblastoma multiforme, IDH, ONC201, ONC206, MGMT, temozolomide, radiotherapyTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - June 4, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on May 20, 2025, titled “Targeting PCNA/AR interaction inhibits AR-mediated signaling in castration resistant prostate cancer cells."In this study, authors Shan Lu and Zhongyun Dong from the University of Cincinnati College of Medicine investigated how interfering with a protein interaction could reduce prostate cancer growth. Their study based on prostate cancer cells shows that blocking the link between PCNA, a protein important for DNA repair, and the androgen receptor (AR), which drives prostate cancer growth, can slow down cancer cell multiplication. This discovery could lead to a new treatment for patients with advanced prostate cancer, particularly those no longer responding to hormone therapy.Prostate cancer is one of the most common cancers in men. Many patients eventually become resistant to hormone treatment. In this advanced stage, called castration-resistant prostate cancer (CRPC), tumors continue to grow by using either the full-length androgen receptor (AR-FL) or altered versions called AR variants (AR-Vs). This study shows that the interaction between AR and PCNA helps both AR-FL and AR-Vs remain active, supporting cancer cell survival and growth.The researchers identified a new region in the AR that binds to PCNA. They developed a small peptide, R9-AR-PIP, to mimic this region and block the AR-PCNA connection. They found that this peptide reduced AR’s ability to bind DNA and lowered the levels of key genes involved in cancer cell growth. Importantly, the peptide was effective against both types of AR, including the variant forms that are especially challenging in CRPC.“We identified a second PIP-box (PIP-box592) in the DNA binding domain of AR and found that dihydrotestosterone enhances the binding of full-length AR (AR-FL) but not a constitutively active variant (AR-V7) to PCNA.”They also tested a small molecule, PCNA-I1S, which interferes with PCNA’s ability to move to the cell nucleus and interact with AR. This molecule showed similar effects as the peptide, reducing AR activity and stopping cancer cell growth. Together, these findings suggest that targeting PCNA/AR interactions could be a promising strategy to fight CRPC, especially in patients with limited treatment options.One key result was that both the peptide and the small molecule reduced the levels of cyclin A2, a protein that helps cells divide and is often overexpressed in CRPC. Since this protein is linked to patients' poor outcomes, its reduction could be especially beneficial.This study improves our understanding of how prostate cancer continues to grow even after hormone treatments fail. By blocking a crucial helper of the androgen receptor, researchers have uncovered a new way to potentially slow or stop the disease. Further studies in animal models are needed, but this approach could lead to more effective treatments for men with advanced prostate cancer.DOI - https://doi.org/10.18632/oncotarget.28722Correspondence to - Zhongyun Dong - dongzu@ucmail.uc.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28722Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, PCNA, androgen receptor, PCNA inhibitors, AR splicing variants, CRPCTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - June 3, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on May 19, 2025, titled “PRDX1 protects ATM from arsenite-induced proteotoxicity and maintains its stability during DNA damage signaling."In this study, led by first author Reem Ali and corresponding author Dindial Ramotar from Hamad Bin Khalifa University in Qatar, researchers discovered that a protein called PRDX1 helps maintain the stability of ATM, a key protein involved in repairing damaged DNA, especially when cells are under stress from arsenite exposure. The study found that without PRDX1, cells lose their ability to repair DNA and become more sensitive to chemotherapy. This finding suggests that targeting PRDX1 could improve the success of some cancer treatments.PRDX1 is already known for its role in protecting cells from oxidative damage, but this study shows it also plays a role in the DNA repair process. ATM is an essential protein that detects breaks in DNA and starts the repair process. When PRDX1 is missing, ATM is rapidly lost, especially when cells are exposed to arsenite, a toxic substance found in the environment. Without ATM, the DNA repair system fails, leaving cells more vulnerable to damage.By using both human cell lines and clinical samples from ovarian cancer patients, the team showed that high levels of PRDX1, along with ATM and MRE11 (another DNA repair protein), were linked to tumors' aggressive features and lower patient survival rates. This pattern suggests that tumors with high PRDX1 may resist chemotherapy by increasing their DNA repair capacity. On the other hand, removing PRDX1 weakened the repair system and made cancer cells more responsive to DNA-damaging platinum drugs.The study also showed that combining low doses of arsenite with drugs that either block ATM or damage DNA caused a much higher rate of cancer cell death in cells that lacked PRDX1. These results suggest a new treatment approach: lowering PRDX1 levels to make cancer cells more sensitive to DNA-damaging platinum therapies already in use. This highlights PRDX1 not only as a protector of cell function but also as a potential weak point in cancer cells.“As such, we propose that small molecule inhibitors of PRDX1, or single nucleotide polymorphisms that compromise PRDX1 function, in combination with low doses of arsenite can be exploited to treat chemo-resistant tumours.”These findings open the door for the use of PRDX1 as a biomarker to predict treatment response and as a promising target for new combination therapies. For patients with ovarian cancer and potentially other tumors, adjusting PRDX1 levels may help overcome drug resistance and improve outcomes.DOI - https://doi.org/10.18632/oncotarget.28720Correspondence to: Dindial Ramotar - dramotar@hbku.edu.qaVideo short - https://www.youtube.com/watch?v=suOhF7mPlNQSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28720Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, redox signaling, homologous recombination, protein interaction, cell cycle, protein modificationTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - May 23, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on May 19, 2025, titled “Immune-mediated adverse events following atezolizumab and bevacizumab in a multinational Latin American cohort of unresectable hepatocellular carcinoma."The study, led by first authors Leonardo Gomes da Fonseca from Hospital das Clínicas, Universidade de São Paulo, Brazil, and Federico Piñero from Hospital Universitario Austral, Argentina, investigated how patients with advanced liver cancer in Latin America respond to a widely used immunotherapy combination. The researchers found that although a minority of patients developed immune-related side effects, these events did not significantly impact overall survival. Their findings highlight the importance of early recognition and careful management of such side effects in real-world clinical settings.Liver cancer is a leading cause of cancer deaths worldwide, with limited treatment options for patients diagnosed at an advanced stage. Immunotherapy, particularly the combination of atezolizumab and bevacizumab, has become a standard approach. However, these treatments can sometimes trigger the body’s immune system to attack healthy organs, leading to what are called immune-related adverse events, or irAEs. Until now, little data existed on how frequently these events occur in Latin American patients and whether they impact treatment outcomes.The researchers followed 99 patients from Argentina, Brazil, Chile, and Colombia, most of whom had cirrhosis or underlying liver disease. They received atezolizumab and bevacizumab for a median duration of six months. The researchers reported that only 18% of the patients experienced immune-related side effects, most commonly affecting the liver (hepatitis) and thyroid (thyroiditis). Most of these cases were mild or moderate, and half of them resolved completely within a month. Only eight patients needed treatment with steroids to control the immune response.Importantly, the occurrence of immune-related side effects did not affect how long patients survived after starting treatment. The median survival was the same—18.5 months—for both those who experienced irAEs and those who did not. This result suggests that while irAEs require careful management, they may not reduce the overall benefits of immunotherapy.Another significant finding was that patients with higher levels of alpha-fetoprotein (AFP), a protein often elevated in liver cancer, were more likely to experience these side effects. This information could help clinicians identify patients who need closer control during treatment.“Notably, baseline alpha-fetoprotein (AFP) values ≥400 ng/ml were significantly associated with the development of irAEs.”The study also points to key differences between clinical trial results and real-world experiences. While clinical trials report higher rates of side effects, this real-world data showed a lower incidence, possibly due to less intensive monitoring or differences in how side effects are documented in everyday practice.In summary, this study highlights that patients require ongoing vigilance and individualized care when treating liver cancer with immunotherapy. It provides valuable information to healthcare providers in Latin America and other regions with similar patient populations, aiming to improve outcomes while minimizing risks.DOI - https://doi.org/10.18632/oncotarget.28721Correspondence to - Federico Piñero - fpinerof@cas.austral.edu.arTo learn more about Oncotarget, please visit https://www.oncotarget.com.MEDIA@IMPACTJOURNALS.COM
Scientists have engineered small, targeted proteins that can penetrate brain cancer cells and prevent them from invading healthy tissue, offering a promising new approach to treating glioblastoma multiforme (GBM), one of the deadliest forms of brain cancer. This strategy was developed by researchers at the University of Nevada, Reno, and published recently in Oncotarget.The Challenge of Treating Glioblastoma MultiformeGlioblastoma is an aggressive and fast-growing brain tumor that infiltrates healthy brain tissue, making complete surgical removal nearly impossible. Standard treatments like chemotherapy and radiation can slow its growth but rarely prevent it from returning. One major reason for this invasiveness is a group of enzymes known as matrix metalloproteinases (MMPs), which break down surrounding tissue to allow cancer cells to spread. Among these, MMP-9 plays a particularly important role in driving tumor progression and resisting existing therapies.Attempts to block MMPs using small-molecule drugs have failed in clinical trials due to problems like poor selectivity and harmful side effects. Researchers have been searching for safer, more targeted methods to interfere with these enzymes and limit glioblastoma’s spread.The Study: Engineered Proteins to Inhibit Tumor InvasionIn the study called “Effect of TIMPs and their minimally engineered variants in blocking invasion and migration of brain cancer cells,” researchers Elham Taheri and Maryam Raeeszadeh-Sarmazdeh investigated tissue inhibitors of metalloproteinases (TIMPs), which are natural blockers of MMPs, and their engineered modified versions made to work better. Specifically, the team studied TIMP-1, TIMP-3, along with two engineered molecules, mTC1 and mTC3, in laboratory cell models of GBM.Full blog - https://www.oncotarget.org/2025/05/21/engineered-proteins-show-promise-in-stopping-glioblastoma-invasion/Paper DOI - https://doi.org/10.18632/oncotarget.28691Correspondence to - Maryam Raeeszadeh-Sarmazdeh - maryamr@unr.eduVideo short - https://www.youtube.com/watch?v=tdBlkOX50D8Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28691Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, TIMP minimal variants, glioblastoma multiforme (GBM), brain cancer, MMP inhibitorsTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - May 21, 2025 – A new #review was #published in Volume 16 of Oncotarget on May 19, 2025, titled “Advancements in bladder cancer treatment: The synergy of radiation and immunotherapy."Researchers from the University of California, Irvine, led by Nazmul Hasan, reviewed recent clinical and scientific advances in combining radiation therapy with immunotherapy for bladder cancer. The article summarizes growing evidence that this combined approach may strengthen the immune response and improve long-term disease control. This strategy is especially important for patients who are not candidates for surgery or who respond poorly to conventional treatments.Bladder cancer is a serious and frequent condition, particularly affecting older men. Traditional treatments—surgery, chemotherapy, and radiation—can be effective, but they often fail to prevent cancer reappearance in advanced cases. The review explores how combining radiation and immunotherapy could improve outcomes by helping the immune system detect and destroy cancer cells more effectively.Radiation therapy destroys cancer cells and triggers the release of tumor signals that attract immune cells. Immunotherapy, including drugs like pembrolizumab and nivolumab, helps the immune system work better by blocking proteins that allow cancer to evade detection. Used together, these treatments may produce a stronger, more widespread anti-tumor effect, even at distant sites not directly targeted by radiation.The review discusses several clinical trials that support this approach. One phase II study reported that combining radiation with the immunotherapy drug durvalumab led to promising survival rates and manageable side effects. Another trial in Australia tested pembrolizumab with radiation and chemotherapy, resulting in high tumor control and extended patient survival. However, the review also points out that other trials showed serious side effects when high doses or multiple immunotherapy drugs were used at once."Joshi et al. performed a phase II study to determine the safety and efficacy of combining radiation therapy with durvalumab, a PD-L1 inhibitor, in patients who were ineligible for surgery or cisplatin-based chemotherapy."While the combination approach is promising, the authors emphasize that more research is needed to refine this treatment strategy. One major challenge is determining which patients are most likely to benefit. Future studies should focus on identifying reliable biomarkers, such as tumor mutation burden or immune activity, to guide personalized treatment plans.This review highlights the potential of combining radiation and immunotherapy to improve outcomes for bladder cancer patients. With continued research and careful treatment design, this approach could offer new treatment options for those facing aggressive or hard-to-treat forms of the disease.DOI - https://doi.org/10.18632/oncotarget.28723Correspondence to - Nazmul Hasan - nhasan1@hs.uci.eduVideo short - https://www.youtube.com/watch?v=AxrZhIUXrOQSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28723Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, bladder cancer, immunotherapy, radiation, microenvironment, abscopalTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY – May 19, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on May 9, 2025, titled “Analytical validation of a circulating tumor DNA assay using PhasED-Seq technology for detecting residual disease in B-cell malignancies.”In this study, a team from Foresight Diagnostics led by first author Nina Klimova and corresponding author Laura Hyland validated a new DNA-based blood test designed to detect minimal residual disease (MRD) in patients with B-cell cancers. This assay uses a highly sensitive method called Phased Variant Enrichment and Detection Sequencing (PhasED-Seq) to find tiny fragments of tumor DNA in the blood. Its ultra-sensitive detection capabilities offer a powerful tool for early cancer detection, monitoring treatment response, and predicting cancer reappearance.B-cell lymphomas, such as diffuse large B-cell lymphoma (DLBCL), are among the most prevalent blood cancers. Although many patients respond to initial treatment, up to 40% relapse. Standard monitoring methods such as imaging scans often miss low levels of cancer cells, creating a need for more precise tools. This study introduces a non-invasive blood test that improves the detection of MRD, a critical factor in guiding follow-up care and early intervention.The test works by tracking unique groups of mutations known as phased variants in tumor DNA. These mutations are more specific to cancer and allow for highly accurate identification of tumor fragments in the bloodstream. The PhasED-Seq-based MRD assay was tested on three types of samples. First, blood plasma from healthy individuals was used to confirm the test does not give false positives. Second, researchers created controlled samples by mixing tumor DNA from lymphoma patients with healthy DNA to measure how sensitive and precise the test is. Finally, blood samples from patients with B-cell lymphoma were used to compare the new test to an existing method.Across all sample types, the PhasED-Seq-based MRD assay demonstrated exceptional performance—capable of detecting fewer than one cancer DNA molecule per million normal DNA fragments. It also demonstrated a very low false positive rate and over 96% reproducibility across different laboratory conditions. Compared to an existing method, the new PhasED-Seq assay showed more than 90% agreement in positive results and nearly 78% agreement in negative results. In cases where the tests disagreed, the new method aligned more closely with actual clinical outcomes, including whether patients relapsed or stayed in remission.“The background error rate of the PhasED-Seq-based MRD assay was 1.95E-08, or 1.95 mutant molecules in 100 million informative molecules.”The findings support the use of PhasED-Seq-based MRD assays in routine clinical practice. It could be especially useful for identifying patients who need additional treatment even when imaging results appear normal. This aligns with updated clinical guidelines that encourage the use of blood-based DNA tests to supplement traditional scans in lymphoma care.This study offers strong evidence that the PhasED-Seq-based MRD assay is a precise, reliable, and clinically relevant tool. By detecting signs of cancer earlier and more accurately, it may help clinicians tailor treatments to individual patients and improve long-term outcomes in B-cell malignancies.DOI - https://doi.org/10.18632/oncotarget.28719Correspondence to - Laura Hyland - laura.hyland@foresight-dx.comVideo short - https://www.youtube.com/watch?v=8hdh3G5zvlcFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - May 14, 2025 – A new #review paper was #published in Volume 16 of Oncotarget on May 9, 2025, titled “Relationship between ABO blood group antigens and Rh factor with breast cancer: A systematic review and meta-analysis."A comprehensive study, led by first authors Rahaf Alchazal from Yarmouk University and Khaled J. Zaitoun from Johns Hopkins University School of Medicine and Jordan University of Science and Technology, examined the potential link between blood type and breast cancer. The research team conducted a systematic review and meta-analysis of 29 previously published studies, involving more than 13,000 breast cancer patients and over 717,000 controls. “Researchers searched for studies on breast cancer patients and ABO blood groups across four major databases: PubMed, Scopus, Web of Science, and Google.“Breast cancer is the most common cancer among women worldwide. Identifying risk factors is vital for early detection and prevention. While many studies have explored lifestyle and genetic causes, this analysis focused on the ABO blood group system. By pooling global data, the researchers found that blood type A was the most common among breast cancer patients and was significantly associated with an 18% increased risk compared to type O.The study did not find a significant association between breast cancer and blood types B, AB, or Rh factor. Although the results do not prove causation, they point to a biological pattern worth further investigation. Blood group antigens are proteins found on the surface of cells, including breast tissue. These molecules may influence how cancer develops and spreads by interacting with the immune system or affecting cell behavior.This meta-analysis is the most extensive review to date on this topic, based on studies conducted across Asia, Europe, Africa, and the Americas. While previous research found unclear conclusions, this large-scale evaluation provides stronger evidence for a possible connection between blood type A and breast cancer risk.Researchers note that regional differences, genetic diversity, and study quality may affect individual results. Nevertheless, the overall trend supports considering blood type A as a potential risk marker. This insight could help shape screening guidelines, encouraging earlier or more frequent checkups for women with this blood type.Further research is needed to understand why blood type A may play a role in cancer development. Future studies may explore genetic mechanisms, immune responses, and other biological pathways. These efforts could lead the way for more personalized cancer prevention and care strategies.DOI - https://doi.org/10.18632/oncotarget.28718Correspondence to - Khaled J. Zaitoun - kzaitou1@jh.eduVideo short - https://www.youtube.com/watch?v=BQFVtreaetISign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28718Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, breast cancer, cancer risk factors, blood group antigens, tumorTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - May 9, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on May 8, 2025, titled “METTL3 promotes oral squamous cell carcinoma by regulating miR-146a-5p/SMAD4 axis."In this study, researchers Jayasree Peroth Jayaprakash, Pragati Karemore, and Piyush Khandelia from the Birla Institute of Technology and Science, India, discovered that a molecule called METTL3 contributes to the development and spread of oral squamous cell carcinoma (OSCC). The study shows that METTL3 increases the levels of a small RNA molecule called miR-146a-5p, which blocks SMAD4, a key tumor-suppressing gene. These findings help explain why oral cancers are difficult to treat and may offer a new target for more effective therapies.Oral squamous cell carcinoma is a common and aggressive cancer affecting the mouth and throat. It has a high death rate, mainly due to late detection, treatment resistance, and the cancer’s ability to invade nearby tissues. In this study, the researchers focused on METTL3, an enzyme that adds chemical tags known as m6A marks to RNA, which change how genetic information is used by cells. They found that METTL3 is unusually active in OSCC cells, causing an increase in miR-146a-5p. This molecule, in turn, blocks the function of SMAD4, which helps control how cells grow and die in our bodies.“METTL3, the primary m6A RNA methyltransferase, is significantly upregulated in OSCC cells leading to increased global m6A levels.”When METTL3 was reduced or chemically blocked, miR-146a-5p levels dropped and SMAD4 levels increased. This shift slowed the growth of cancer cells, increased their death, and made them less likely to spread. When researchers reintroduced miR-146a-5p or lowered SMAD4 levels again, the cancer-promoting behavior returned. These results show that the METTL3–miR-146a-5p–SMAD4 pathway plays a key role in OSCC.The findings open up new possibilities for treatment. Drugs that block METTL3 or miR-146a-5p or that restore SMAD4 could slow or stop tumor growth. One such drug, STM2457, which targets METTL3, has already shown promise in lab studies. As research progresses, targeting this molecular pathway may offer a new strategy in treating OSCC.This discovery improves our understanding of how OSCC develops and avoids the body’s defenses. By interfering with this newly discovered pathway, future treatments may become more successful, improving survival rates and quality of life for people with this disease.DOI - https://doi.org/10.18632/oncotarget.28717Correspondence to - Piyush Khandelia - piyush.khandelia@hyderabad.bits-pilani.ac.inVideo short - https://www.youtube.com/watch?v=o5XuDlcIma8Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28717Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
A recent #study from Assiut University Hospital in Egypt, published in #Oncotarget, presents a promising strategy for patients with metastatic #colorectalcancer (mCRC). The #research introduces a gentler yet effective maintenance therapy that may extend survival, enhance quality of life, and offer a more accessible treatment option for mCRC patients worldwide.The Challenge of Treating Metastatic Colorectal CancerColorectal cancer is one of the most common causes of cancer-related deaths worldwide. When it spreads to other parts of the body—a stage known as mCRC—it becomes much more difficult to treat. At this stage, clinicians often use strong drug combinations like FOLFOX or CAPOX, which mix chemotherapy drugs to stop cancer growth. FOLFOX combines three drugs given intravenously, while CAPOX includes two of the same drugs, with one taken as a pill.While effective, these treatments can cause serious side effects. For example, one of the main drugs, oxaliplatin, can lead to nerve damage, making it painful or difficult to use the hands and feet. Fatigue, diarrhea, and other issues are also common. Over time, these side effects may force clinicians to stop or adjust the treatment, even if it is working.That is where maintenance therapy comes in. After the cancer is controlled, clinicians often switch to a gentler treatment plan to keep it from returning. The challenge is finding a therapy that continues to work without causing too many side effects, especially in places where access to expensive or intensive treatments is limited.Full blog - https://www.oncotarget.org/2025/05/07/panitumumab-and-low-dose-capecitabine-a-promising-maintenance-therapy-for-metastatic-colorectal-cancer/Paper DOI - https://doi.org/10.18632/oncotarget.28687Correspondence to - Doaa A. Gamal - doaaalygamaal@gmail.comVideo short - https://www.youtube.com/watch?v=wuPSS0EdK-8Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28687Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, Panitumumab, maintenance, colorectal cancer, CapecitabineAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - May 5, 2025 – Oncotarget, #published by Impact Journals, is proud to #announce its presence as an #exhibitor at the 47th Annual Meeting of the Society for Scholarly Publishing (SSP), taking place May 28–30, 2025, at the Hilton Baltimore in Maryland. Impact Journals publishes scholarly journals in the biomedical sciences, with a focus on cancer and aging research.Attendees are invited to stop by Booth #209 to meet members of the Oncotarget team and learn more about the journal’s latest initiatives. This year’s conference theme, “Reimagining the Future of Scholarly Publishing at the Intersection of Value and Values,” highlights critical topics such as artificial intelligence, research ethics, and transparency in science—principles that closely align with Oncotarget's commitment to rigorous peer review and scientific integrity.We look forward to connecting with SSP attendees to discuss Oncotarget’s mission, explore potential collaborations, and emphasize the role of open science in advancing cancer research and related fields.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us on social media at:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - April 28, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on April 24, 2025, titled “PD-L1 and FOXP3 expression in high-grade squamous intraepithelial lesions of the anogenital region."Researchers Humberto Carvalho Carneiro, Rodrigo de Andrade Natal, José Vassallo and Fernando Augusto Soares from the Instituto D’Or de Pesquisa e Ensino and Rede D’Or studied early tissue changes caused by human papillomavirus (HPV) in the anal, vulvar, and penile regions. They found that high-grade pre-cancer lesions triggered stronger immune responses and showed higher levels of two immune-related markers, PD-L1 and FOXP3. These findings are important because they help explain how some HPV-related lesions progress to cancer while others heal on their own.High-risk HPV is known to cause several types of anogenital cancers. Before these cancers appear, the virus often leads to abnormal tissue changes known as high-grade squamous intraepithelial lesions. Many of these lesions disappear without treatment, but some become cancer—especially in people with weakened immune systems. This study explored how immune activity may play a role in this progression.The researchers examined tissue from 157 patients—95 males and 55 females—with either high-grade or low-grade HPV-related lesions. They found that T-regulatory cells, marked by the FOXP3 protein, were more common in high-grade lesions. These immune cells are known to suppress immune responses, which can allow infected or abnormal cells to grow. The team also found higher expression of PD-L1, a protein that helps cells evade immune detection, particularly in inflammatory immune cells."Dense inflammatory infiltrates and high counts of FOXP3+ cells were significantly more frequent in patients with HSILs than in those with LSILsHR (p = 0.04 and 0.02, respectively). HSILs also exhibited higher PD-L1 expression (padj < 0.01 and < 0.01 for the SP142 and 22C3 clones, respectively), based on the Poisson generalized linear model.”These findings suggest that HPV may begin avoiding the immune system early in infection, even before cancer develops. The combination of high FOXP3 and PD-L1 levels may create a protective environment for infected cells, making them harder for the body to eliminate. This immune evasion may allow the lesions to remain and, over time, become cancerous.The study also compared patients with and without HIV to assess whether immune health influenced the results. While those with compromised immune systems had more extensive lesions, PD-L1 and FOXP3 expression was also found in patients with healthy immune systems. This evidence shows that immune evasion by HPV can happen regardless of a person’s immune status.Understanding how PD-L1 and FOXP3 function in early HPV-related lesions may help clinicians predict which lesions are more likely to become cancer. These insights could lead to new strategies for monitoring, treating, or preventing HPV-related precancerous lesions and cancer in the anogenital region. The study highlights how early immune system changes can play a key role in the development of HPV-related cancers.DOI - https://doi.org/10.18632/oncotarget.28715Correspondence to - Humberto Carvalho Carneiro - humberto.carneiro@rededor.com.brVideo short - https://www.youtube.com/watch?v=6d8G8TUbgYcSubscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
A new study from the Sidney Kimmel Comprehensive Cancer Center and Johns Hopkins University School of Medicine, published in Oncotarget, reveals that the gene p53, long known as the “guardian of the genome,” may be even more powerful than previously thought. By studying it in non-cancerous human cells, researchers discovered how p53 stops risky cell growth and uncovered two new potential targets for cancer therapy.Understanding p53: The Genome’s Guardian Against CancerThe p53 gene is one of the most important natural defenses our body has against cancer. When functioning properly, p53 detects damage in a cell’s DNA and either stops the cell from dividing or pushes it to self-destruct. This process helps prevent potentially dangerous mutations from spreading. However, many cancers find ways to silence or mutate p53, allowing uncontrolled growth and resistance to treatments.Studying p53 in a clear and accurate way has long been a challenge. Most cancer cell models used in research already carry numerous genetic mutations, which can mask or alter how p53 truly functions. To fully understand this vital tumor-suppressing gene, scientists needed a model that closely resembled healthy, genetically stable human cells—yet could still be maintained and studied over time in the laboratory.The Study: Exploring p53 in Normal and Cancer Cell ModelsResearchers Jessica J. Miciak, Lucy Petrova, Rhythm Sajwan, Aditya Pandya, Mikayla Deckard, Andrew J. Munoz, and Fred Bunz explored p53 activity using a uniquely suitable cell line: hTERT-RPE1. These non-cancerous human cells are immortalized using telomerase, meaning they continue dividing like cancer cells, but without the chaotic mutations seen in tumors. This makes them an excellent model for studying how p53 operates in near-normal conditions.Full blog - https://www.oncotarget.org/2025/04/22/new-insights-into-p53-a-powerful-genes-role-in-cancer-therapy/Paper DOI - https://doi.org/10.18632/oncotarget.28690Correspondence to - Fred Bunz - fredbunz@jhmi.eduVideo short - https://www.youtube.com/watch?v=Psxj3ctbTukSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28690Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, p53, ionizing radiation, immortalized cells, ALDH3A1, NECTIN4About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - April 15, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on April 4, 2025, titled “Association between two single nucleotide polymorphisms of the Prostaglandin-Endoperoxide Synthase 1 and 2 genes and cell proliferative prostatic diseases in Lebanon."The team of researchers led by first author Brock J. Sheehan and corresponding author Ruhul H. Kuddus, from Utah Valley University, discovered that a specific genetic variation in the PTGS2 gene is associated with a higher risk of benign prostate hyperplasia (BPH), a common condition in aging men. The study, which focused on Lebanese men, suggests that the C allele of the -765 G>C polymorphism in the PTGS2 gene may increase risk to this non-cancerous but problematic prostate condition. This finding could help identify men at greater risk earlier and lead to better treatment choices.Benign prostate hyperplasia and prostate cancer are two common conditions that involve abnormal cell growth in the prostate gland. While prostate cancer is malignant and potentially life-threatening, BPH is a non-cancerous enlargement that can still significantly affect quality of life. Both conditions are widespread in older men, with BPH affecting over 70% of men above 60. Researchers have long suspected that inflammation-related genes may play a role in their development. In this study, the focus was to study PTGS1 and PTGS2, genes that help produce enzymes involved in inflammation.Using DNA samples from 168 Lebanese men, including 61 with prostate cancer, 51 with BPH, and 56 healthy controls, the researchers analyzed two common gene variants. They found no link between the PTGS1 variant and either condition. However, the PTGS2 variant showed a strong association with BPH. Men carrying the C version of this gene were more than twice as likely to have BPH compared to those without it. While a similar trend was observed in men with prostate cancer, the results were less conclusive."The C allele of SNP-765G>C of the PTGS2 gene was significantly associated with an increased risk of BPH (OR = 2.30, p-value = 0.01)."This is the first study to report a genetic link between the C allele of the -765 G>C polymorphism in the PTGS2 gene and BPH in Lebanese men. It builds on earlier findings that associated this gene variant with various cancers, including prostate, colon, and stomach cancers. Although based on a relatively small and specific population, the study offers new insight that could help improve genetic screening and guide prevention strategies.The research also points to the potential benefits of COX-2 inhibitors—drugs already used to treat prostate conditions—which may be more effective for men with certain PTGS2 gene types. Further studies in larger and more diverse groups are needed to confirm these results and explore how this gene variant influences prostate disease. In the future, simple genetic tests could help identify men at higher risk before symptoms appear, allowing for earlier and more personalized care.Continue reading: DOI: https://doi.org/10.18632/oncotarget.28710Correspondence to: Ruhul H. Kuddus — ruhul.kuddus@uvu.eduSubscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - April 11, 2025 – A new research perspective was published in Oncotarget, Volume 16, on April 4, 2025, titled “GSK3β activation is a key driver of resistance to Raf inhibition in BRAF mutant melanoma cells."In this work, first author Diana Crisan and corresponding author Abhijit Basu from the University Hospital Ulm led a team that presents experimental evidence pointing to the protein GSK3β as a key contributor to drug resistance in melanoma. Their findings suggest that GSK3β becomes increasingly active in cancer cells during treatment, helping them survive and adapt despite ongoing therapy with BRAF inhibitors.Melanoma is a type of skin cancer in which nearly half of patients have mutations in the BRAF gene that accelerate tumor growth. While treatments targeting BRAF, known as BRAF inhibitors, initially work well, tumors often find ways to fight back. This research perspective explores how GSK3β, a protein involved in metabolism and cell survival, becomes more active in melanoma cells that develop resistance to BRAF inhibitors.Researchers treated melanoma cells with a common BRAF mutation using Dabrafenib, a widely used BRAF inhibitor. Over time, the cancer cells developed resistance and showed a marked increase in GSK3β levels. This pattern was confirmed across multiple melanoma cell models, suggesting that the finding is consistent and reliable.Importantly, the researchers observed that treating resistant cancer cells with a GSK3β inhibitor significantly reduced their growth. This result suggests that blocking this protein could restore sensitivity to treatment, highlighting GSK3β as a promising therapeutic target and supporting the idea of combining GSK3β inhibitors with existing melanoma therapies.“Remarkably, treatment of BRAFi-resistant melanoma cells with the GSK3 inhibitor LY2090314 for three weeks could overcome resistance and significantly decreased melanoma cell growth, confirming the causal role of GSK3 activation for BRAFi resistance development.”The research perspective adds to ongoing efforts to understand and overcome melanoma drug resistance. It shows that resistance is not driven only by genetic mutations but may also involve adaptive changes in the cell’s internal signaling and survival mechanisms. By identifying GSK3β as a potential contributor, the authors offer a new direction for improving the durability of targeted treatments in melanoma.As research continues, GSK3β may be a critical factor in the long-term success of melanoma therapy, particularly for patients who have stopped responding to standard BRAF-targeted drugs.Continue reading: DOI: https://doi.org/10.18632/oncotarget.28711Correspondence to: Abhijit Basu — abhijit.basu@alumni.uni-ulm.deVideo short - https://www.youtube.com/watch?v=G2Tq4_r6xLwSubscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
Despite decades of research, treatment for osteosarcoma has remained largely unchanged, especially for patients whose cancer spreads or returns. However, a growing body of evidence, summarized in the review “SETDB1 amplification in osteosarcomas: Insights from its role in healthy tissues and other cancer types,” published in Oncotarget, highlights the gene regulator SETDB1 as a potential key player in cancer progression, immune system evasion, and resistance to therapy. Targeting this protein may offer a new direction for developing more effective treatments.Understanding OsteosarcomaOsteosarcoma is a rare but aggressive bone cancer that primarily affects teenagers and young adults. While current treatments like surgery and chemotherapy can help some patients, outcomes are much worse for those with relapsed or advanced disease.One of the reasons osteosarcomas are so difficult to treat is their complex and unstable genetics. Unlike cancers with well-defined mutations, osteosarcomas involve chaotic DNA rearrangements, making it difficult to identify precise drug targets. Adding to the challenge, the immune system often fails to recognize these cancer cells, limiting the success of immunotherapy.Full blog - https://www.oncotarget.org/2025/04/09/targeting-setdb1-a-new-strategy-for-treating-osteosarcoma/Paper DOI - https://doi.org/10.18632/oncotarget.28688Correspondence to - Antonin Marchais - antonin.marchais@gustaveroussy.fr, and Maria Eugenia Marques Da Costa - jenny.marquescosta@gustaveroussy.frVideo short - https://www.youtube.com/watch?v=f9WgaDoEubsSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28688Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, SETDB1, cancer epigenetics, tumor immunogenicity, mesenchymal differentiation in osteosarcomaAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - April 8, 2025 – A new #editorial was #published in Oncotarget, Volume 16, on April 4, 2025, titled “Deep learning-based uncertainty quantification for quality assurance in hepatobiliary imaging-based techniques."Dr. Yashbir Singh from Mayo Clinic and his colleagues discussed how artificial intelligence (AI) can improve liver imaging by recognizing when it might be wrong. This approach, called “uncertainty quantification,” helps clinicians better detect liver cancer and other diseases by pointing out areas in medical scans that need a second look. The authors explain how these AI tools could make imaging results more accurate and reliable, which is especially important when diagnosing serious conditions like liver tumors.Liver and bile duct imaging is difficult because of the organ’s complex structure and differences in image quality. Even skilled radiologists can struggle to identify small or hidden tumors, especially in patients with liver damage or scarring. The editorial explains how new AI models not only read medical images but also measure their own confidence. When the AI system is unsure, it can alert clinicians to take a closer look. This extra layer of information can reduce missed diagnoses and improve early detection of liver cancer.One of the most advanced tools described in the editorial is called AHUNet (Anisotropic Hybrid Network). This AI model works with both 2D and 3D images and can highlight which parts of a scan it is most confident about. It performed well when measuring the entire liver and showed how its confidence dropped when scanning smaller or multiple lesions. This feature helps clinicians know when more testing or review is needed.The authors also looked at other AI models used in liver imaging. Some tools were able to analyze liver fat using ultrasound images and give clinicians both a result and a confidence score. Others improved the speed and accuracy of liver magnetic resonance imaging (MRI) scans, helping to create clear images in less time. These advancements could help hospitals work faster and provide better care.The editorial highlights how this technology can be especially helpful in smaller clinics. If they do not have liver specialists, they could still use AI systems that flag uncertain results and send them to larger centers for review. Such an approach could improve care in rural or less-resourced areas.“Radiology departments should develop standardized reporting templates that incorporate uncertainty metrics alongside traditional imaging findings.”By using AI tools that know when to second-guess themselves, clinicians may soon have more reliable methods for detecting liver cancer and monitoring liver disease. The authors suggest that uncertainty-aware AI may soon become a vital part of everyday medical imaging, supporting faster and more accurate decisions in liver disease care.DOI: https://doi.org/10.18632/oncotarget.28709Correspondence to: Yashbir Singh — singh.yashbir@mayo.eduVideo short - https://www.youtube.com/watch?v=Zm0QASQ_YSISign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28709Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords: cancer, deep learning, uncertainty quantification, radiology, hepatobiliary imagingTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY - April 4, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on March 27, 2025, titled “Imipridones ONC201/ONC206 + RT/TMZ triple (IRT) therapy reduces intracranial tumor burden, prolongs survival in orthotopic IDH-WT GBM mouse model, and suppresses MGMT."Researchers from Brown University, led by first author Lanlan Zhou and corresponding author Wafik S. El-Deiry, have shown that combining a new class of drugs called imipridones with standard glioblastoma treatments significantly improves outcomes in mice. The study tested ONC201 and its analog ONC206 in combination with radiation therapy and the chemotherapy drug temozolomide (TMZ), a regimen referred to as IRT. This triple therapy slowed tumor growth and extended survival in a mouse model of glioblastoma, offering a potential new strategy for one of the most aggressive and treatment-resistant brain cancers.Glioblastoma is a fast-growing brain tumor with a poor prognosis and limited treatment options. Standard care typically includes surgery, radiation, and TMZ, but most patients still face a short life expectancy. While ONC201 and ONC206 are currently being studied in clinical trials as single agents, there has been limited information on how they interact with standard therapies. This study is the first to show that both drugs work synergistically with radiation and TMZ, strengthening their overall effects.The results showed that in both laboratory-grown tumor cells and mice, the triple therapy significantly slowed cancer cell growth, reduced tumor size, and prolonged survival compared to using any single or double treatment. Mice treated with IRT lived an average of 123 days, with some surviving more than 200 days—far longer than the 44 to 103 days observed with other treatment combinations. In addition to directly killing tumor cells, ONC201 and ONC206 lowered the expression of MGMT, a protein that helps tumors resist chemotherapy, making the treatment more effective.The researchers also found that the triple therapy reshaped the tumor environment. It decreased levels of harmful molecules that promote tumor growth and immune evasion while increasing signals that activate the immune system. This dual action—directly attacking tumors and boosting immune responses—adds to the potential impact of this treatment approach.“Overall, our preclinical findings support further exploration of the ONC201 and ONC206 IRT regimen as a potential treatment for GBM and diffuse gliomas with H3K27M mutations.”While these findings are based on preclinical mouse models, they offer strong support for advancing this triple therapy to clinical trials. ONC201 and ONC206 are promising due to their ability to cross the blood-brain barrier and enhance the effects of standard treatment. This combination could lead to more effective therapies for glioblastoma and other hard-to-treat brain tumors.DOI - https://doi.org/10.18632/oncotarget.28707Correspondence to - Wafik S. El-Deiry - wafik@brown.eduVideo short - https://www.youtube.com/watch?v=Q_mXy8mana0Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28707Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - March 31, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on March 21, 2025, titled “FGR Src family kinase causes signaling and phenotypic shift mimicking retinoic acid-induced differentiation of leukemic cells."A research team led by first author Noor Kazim and corresponding author Andrew Yen from Cornell University discovered that the FGR protein—traditionally considered a cancer-promoting molecule—can instead trigger leukemia cells to mature. This effect mirrors the response usually induced by retinoic acid (RA); a compound derived from vitamin A that is widely used in cancer therapy. Their finding presents a potential new path for therapies targeting acute myeloid leukemia (AML) and related cancers.Acute myeloid leukemia is often treated using RA-based therapies that force immature white blood cells to mature, slowing their rapid growth. Retinoic acid works through complex signaling and gene regulation involving a group of proteins that orchestrate this transformation. In this study, the team used HL-60 cells, a model for human leukemia, and engineered them to express FGR. Surprisingly, the presence of FGR alone was enough to make these cells mature in a way almost identical to what happens with RA treatment. They began producing well-known markers of maturation such as CD38 and CD11b, generated reactive oxygen species (ROS), and expressed the inhibitor of the cell cycle, p27, all signs that the cells had shifted from a cancer-like, fast-dividing state to a more specialized, mature form. Further analysis revealed that FGR activated a group of proteins known as the "signalsome," which helps trigger the changes needed for cells to differentiate. This same group is typically activated by RA. “Notably, FGR induces the expression of genes targeted by RAR/RXR, such as cd38 and blr1, even without RA."To test its potential use in treatment-resistant leukemias, the researchers introduced FGR into RA-resistant HL-60 cells. In these, FGR did not cause the same maturation process, which suggests that there are other problems with cell signaling that stop both the RA and FGR pathways. This result highlights the complexity of resistance mechanisms and the need for additional research.These findings challenge the traditional view of FGR as strictly a cancer-driving protein. Instead, in this specific context, it appears to initiate anti-cancer behavior. That a single protein can reproduce the effects of a complex therapeutic compound like RA is both surprising and promising. If future research confirms this study's results in more advanced models, FGR could become a new tool for developing therapies for AML and potentially other blood cancers.DOI - https://doi.org/10.18632/oncotarget.28705Correspondence to - Andrew Yen - ay13@cornell.eduVideo short - https://www.youtube.com/watch?v=v2fjeFFoUPQSubscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - April 2, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on March 21, 2025, titled “NSD2-epigenomic reprogramming and maintenance of plasma cell phenotype in t(4;14) myeloma."Researchers Andrea Gunnell, Scott T. Kimber, Richard Houlston, and Martin Kaiser from The Institute of Cancer Research, London, studied how a gene called NSD2 affects the behavior of multiple myeloma (MM) cells. Their findings reveal that NSD2 plays a key role in helping cancer cells retain their identity as plasma cells—white blood cells that normally help the immune system fight infections. This discovery could shape future treatment strategies for patients with a high-risk form of MM known as t(4;14) myeloma.Multiple myeloma is a type of blood cancer that begins in plasma cells found in the bone marrow. About 20% of patients have a genetic change called t(4;14), which makes the NSD2 gene highly active. The research team compared two types of myeloma cells: one with high NSD2 activity and one where NSD2 was turned off. They found that when NSD2 is active, it changes how DNA is folded and how genes are switched on or off, especially genes that help the cells act like plasma cells. When NSD2 was turned off, important markers like CD38 were reduced, and other genes normally silent in plasma cells were activated.The study indicated that NSD2 does not directly affect the main genes responsible for plasma cell creation. Instead, it influences many other genes that help maintain the cancer cell’s identity, which contributes to cancer growth and survival. The researchers also observed physical changes in the cancer cells. Cells with active NSD2 looked and behaved more like typical plasma cells, while cells without NSD2 appeared more immature and lost important surface markers. These changes were linked to differences in how the DNA was organized inside the cells.These findings are especially important as new drugs are being developed to block NSD2. The study suggests that turning off NSD2 could change how MM cells respond to existing treatments. For example, if NSD2 is blocked and CD38 levels drop, the change might affect therapies that target CD38. However, the rise of other immune-related genes might make certain immunotherapies more effective.“Identifying the biological consequences of NSD2 over-expression in MM is not only relevant to informing new therapeutic interventions through indirect targeting of downstream effectors, but also to anticipate possible consequences of targeting NSD2 directly.”In summary, this study shows how NSD2 helps myeloma cells keep their cancerous identity by reorganizing the DNA and influencing gene activity. Understanding this role could help researchers design better treatment approaches and possibly overcome resistance to current therapies in t(4;14) myeloma.DOI - https://doi.org/10.18632/oncotarget.28706Correspondence to - Andrea Gunnell - andrea.gunnell@icr.ac.ukVideo short - https://www.youtube.com/watch?v=hibkjUpRq7ISubscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
A young woman beat leukemia; however, nine years later, she faced a different blood cancer. This rare twist, reported recently in Oncotarget, reveals an unexpected risk of bone marrow transplants and opens new questions about long-term outcomes and donor screening.Bone Marrow TransplantBone marrow transplants, also known as hematopoietic stem cell transplants, are often lifesaving for patients with blood cancers like leukemia. These transplants replace a patient’s damaged bone marrow with healthy cells from a donor, giving the body a fresh start. While this treatment can be remarkably effective, it comes with complex risks. Relapse of the original cancer is the most feared outcome. But in very rare cases, a different threat emerges; a cancer formed from the donor’s cells. This condition, called donor cell–derived hematologic neoplasm (DCHN), occurs in less than 1% of cases, and it can emerge years after a transplant.The Case Report Dr. Aleksandra Mroczkowska-Bękarciak and Dr. Tomasz Wróbel from Wroclaw Medical University in Poland recently published a new DCHN case report, titled “A case report of donor cell–derived hematologic neoplasms 9 years after allogeneic hematopoietic cell transplantation,” in Volume 16 of Oncotarget.Full blog - https://www.oncotarget.org/2025/03/26/when-the-cure-becomes-the-cause-a-rare-case-of-cancer-from-donor-cells/Paper DOI - https://doi.org/10.18632/oncotarget.28686Correspondence to - Aleksandra Mroczkowska-Bękarciak - omroczkowska@interia.plVideo short - https://www.youtube.com/watch?v=G2zd0UqWzeESign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28686Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, hematology, donor cell-derived hematologic neoplasms, geneticsAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - March 25, 2025 – A new #review was #published in Oncotarget, Volume 16, on March 13, 2025, titled “Signaling pathway dysregulation in breast cancer."In this review article, Dinara Ryspayeva and colleagues from Brown University provide a detailed look at how breast cancer cells change the way they communicate and grow—helping tumors survive, spread, and resist treatment. The review highlights how certain gene mutations and disrupted signaling pathways influence therapy response across different types of breast cancer. It also outlines current treatment strategies and clinical trials, offering insights that could improve care for patients with aggressive or hard-to-treat cancers.Breast cancer is the most common cancer in women and a major cause of cancer-related deaths worldwide. While many patients respond to treatment at first, some cancers return or stop responding. The review explores how signaling disruptions inside tumor cells are often behind these setbacks.The authors discuss several major pathways involved in breast cancer, including PI3K/Akt/mTOR, RAS/RAF/MEK/ERK, HER2, Wnt/β-catenin, Notch, NF-κB, and the DNA damage response (DDR). These pathways help control cell growth, division, DNA repair, and survival. When altered by mutations or other changes, they can promote tumor progression and resistance to treatment.One of the most disrupted pathways is PI3K/Akt/mTOR. It plays a central role in cell growth, but in many breast cancers—especially hormone receptor-positive and HER2-positive types—it becomes overactive due to gene mutations, or the loss of a tumor-suppressing protein called PTEN.“Up to 25–40% of BC cases exhibit variations that hyperactivate the PI3K/Akt/mTOR pathway, underscoring its critical role in oncogenesis.”Another key pathway, RAS/RAF/MEK/ERK, can also promote tumor growth. Even without mutations, it may become active when primary pathways are blocked, particularly in HER2-positive and triple-negative breast cancers.The review also highlights several new and emerging treatments aimed at blocking down these signaling pathways. Some drugs are already approved, while others are in clinical trials. The authors suggest that combining different treatments may help stop multiple pathways at once, making it harder for cancer cells to adapt. Matching treatments to each tumor’s unique genetic changes could also improve patient outcomes.This comprehensive review gives researchers and clinicians a clearer understanding of how breast cancer resists treatment and where future therapies should focus. A better understanding of these disrupted signaling systems could lead to more personalized and effective treatments for patients facing aggressive or recurring disease.DOI - https://doi.org/10.18632/oncotarget.28701Correspondence to - Dinara Ryspayeva - dinara_ryspayeva@brown.eduVideo short - https://www.youtube.com/watch?v=ppFVGwdztHISubscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - March 21, 2025 – A new #editorial was #published in Oncotarget, Volume 16, on March 13, 2025, titled “No disease left behind."In this editorial, Dr. Muzamil Arshad from the University of Chicago Medical Center and colleagues highlight a growing concern in cancer care: radiotherapy may leave behind microscopic cancer even when scan images suggest the tumor is gone. The authors argue that this “residual disease” is more common than expected and is linked to worse long-term outcomes. Their perspective calls for a rethinking of how treatment success is judged and how cancer is followed up after therapy.Radiotherapy, especially a form known as stereotactic ablative radiotherapy (SABR), is widely used to treat cancers in the lung, liver, prostate, and other organs. SABR delivers high-dose radiation with outstanding precision and often shows excellent results on scans. However, the authors highlight that relying only on imaging may not provide a complete picture. Months or even years later, follow-up biopsies frequently reveal cancer cells that scan imaging tests were unable to identify.“Residual cancer is identified on histology in 40% of lung, 57–69% of renal cell, 7.7–47.6% of prostate and 0–86.7% of hepatocellular carcinoma.”This gap between what scans show and what tissue analysis finds can have serious consequences. Studies across several cancer types have shown that patients with residual disease—even if small—are more likely to experience cancer recurrence and shorter survival. This pattern holds true for rectal, cervical, prostate, and liver cancers, among others. In some cases, not destroying the tumor completely may allow it to spread to distant organs.The authors point out that a complete response on scan imaging does not necessarily indicate the complete disappearance of the tumor. This mismatch can mislead both clinicians and patients into thinking treatment was more successful than it truly was. The editorial encourages more regular use of biopsy-based tests and new strategies to increase the true effectiveness—or “ablative power”—of SABR.They also discuss promising approaches to improve outcomes, including increasing radiation doses and combining radiotherapy with other therapies, such as immune checkpoint inhibitors. While some trials have shown better tumor control with these combinations, results have not been consistent, and more research is needed to refine these strategies.In summary, this editorial encourages the cancer care community to look beyond the scan images. Residual cancer may remain even when imaging looks clear, and recognizing this hidden threat is key to improving long-term outcomes. The goal is not just to shrink tumors on screen but to fully eliminate the disease.DOI - https://doi.org/10.18632/oncotarget.28700Correspondence to - Muzamil Arshad - muzamil.arshad@uchicagomedicine.orgVideo short - https://www.youtube.com/watch?v=XC0XNjJjC2oSubscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - March 18, 2025 – A new precision oncology paper was #published in Oncotarget, Volume 16, on March 12, 2025, titled “Worldwide Innovative Network (WIN) Consortium in Personalized Cancer Medicine: Bringing next-generation precision oncology to patients."Led by Oncotarget Editor-in-Chief Dr. Wafik S. El-Deiry and a global team of researchers, this special publication highlights the groundbreaking work of the Worldwide Innovative Network (WIN) Consortium, a global collaboration dedicated to transforming cancer care through personalized medicine. By leveraging artificial intelligence (AI), molecular profiling, and innovative clinical trials, WIN is helping clinicians tailor treatments to each patient’s unique cancer profile—moving beyond the traditional one-size-fits-all approach.The WIN Consortium is a fast-moving, non-profit organization bringing together nearly 40 academic, industry, and research institutions, along with patient advocacy groups, across 18 countries and five continents. Founded in 2010 in France by Dr. John Mendelsohn (MD Anderson Cancer Center) and Dr. Thomas Tursz (Gustave Roussy), WIN has been led by different renowned experts. Currently under Dr. El-Deiry’s leadership, WIN continues to break barriers in cancer research, ensuring cutting-edge treatments reach patients worldwide.“The WIN global consortium is ready to take up the challenge by bringing the best possible Precision Oncology trial to patients.”One of WIN’s most significant contributions is the development of N-of-1 clinical trials, a revolutionary approach that personalizes cancer treatment based on a patient’s specific tumor characteristics. Unlike traditional trials that test drugs on large groups, N-of-1 trials focus on finding the best therapy for an individual patient using AI-driven algorithms, genomic analysis, and real-world data. WIN’s WINTHER trial was one of the first to use both DNA and RNA analysis to match patients with the most effective therapies, while the WINGPO trial builds on this approach by integrating AI and liquid biopsies to refine treatment selection. These innovations are helping clinicians make more precise treatment decisions and improving outcomes for cancer patients.While advancing research, the WIN Consortium is also addressing major challenges in precision oncology, including drug accessibility, regulatory barriers, and disparities in global healthcare. By working closely with governments, pharmaceutical companies, and advocacy organizations, WIN is aiming to ensure that life-saving treatments are accessible to all patients, regardless of location or financial status.WIN’s mission is clear: to accelerate the future of precision oncology by delivering the latest scientific advancements into real-world cancer care. As the field continues to evolve, WIN remains at the forefront, developing next-generation trials and leveraging AI-driven insights to improve patient outcomes. Through global collaboration and groundbreaking research, the WIN Consortium is shaping a future where every cancer patient receives the most effective, personalized treatment possible.DOI - https://doi.org/10.18632/oncotarget.28703Correspondence to - Wafik S. El-Deiry - wafik@brown.eduVideo short - https://www.youtube.com/watch?v=XAdYfFoMvUMAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com.MEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - March 17, 2025 – Impact Journals (Oncotarget’s publisher), is pleased to announce its participation as an exhibitor at the American Association for Cancer Research (AACR) Annual Meeting 2025. The meeting is scheduled for April 25-30, 2025, at the McCormick Place Convention Center in Chicago, Illinois.The 2025 AACR Annual Meeting's central theme, "Unifying Cancer Science and Medicine: A Continuum of Innovation for Impact," highlights major breakthroughs and innovative developments transforming cancer research. Oncotarget aligns directly with this vision, being always committed to rapidly publishing and disseminating impactful research findings across diverse areas of cancer science and thus advancing cancer treatment and patient care.Conference attendees are warmly invited to visit Booth 2815 to meet members of the Oncotarget, discover notable recent publications, and discuss collaborative opportunities. Oncotarget, assisted by its publisher Impact Journals, remains focused on accelerating the sharing of crucial oncology research, fostering innovation, and maintaining excellence in cancer research.About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY – March 12, 2025 – A new #editorial was #published in Oncotarget, Volume 16, on March 10, 2025, titled “COMETgazing – interesting insights, lessons for clinical practice and a call for more precision using the biomarkerSCOPE.”Dr. Mangesh A. Thorat, affiliated with Queen Mary University of London, Homerton University Hospital, and King’s College London, discusses new findings suggesting that some women diagnosed with early-stage breast cancer may not need immediate surgery. The editorial is based on results from the COMET trial, which studied women with low- to intermediate-grade ductal carcinoma in situ (DCIS). The findings raise questions about the necessity of surgery and highlight the importance of more precise screening methods for DCIS, ensuring that only those who truly need treatment receive it.Breast cancer screening programs are designed to detect cancer early, but this editorial reinforces the concern that some detected cancers may never become a real threat. The COMET trial compared two strategies for treating breast cancer: standard treatment, which includes surgery and possible additional therapy, versus active monitoring, where patients are closely observed without immediate intervention.The results indicate that many of the invasive cancers diagnosed in the monitoring group were likely present from the start rather than developing from DCIS over time. Dr. Thorat points out that these invasive cancers were often slightly larger, but they did not appear to be aggressive. These findings challenge the assumption that immediate treatment is necessary for all cases of DCIS. Researchers estimate that at least half of the invasive breast cancers in this study either take years to progress or may never progress at all.“The planned long-term follow-up of the trial may shed more light on the median length of lead-time and the proportion of IBCs regressing as well as DCIS progression under different lead-time assumptions.”Current methods for evaluating DCIS rely heavily on histological grading, which has limitations. Dr. Thorat emphasizes the need for more precise tools to determine which DCIS cases require treatment. His previous research suggests that biomarkers, such as multi-clonal estrogen receptor (ER) expression and tumor-infiltrating lymphocytes (TILs), may help predict which DCIS cases are truly at risk of becoming invasive.The editorial also highlights that many women prefer to avoid surgery when possible. In a related study, only 52% of patients in the standard care group followed through with it, indicating that more individuals are willing to consider alternatives to surgery. This fact underscores the importance of developing accurate biomarkers to guide treatment decisions and ensure that patients receive appropriate care without unnecessary interventions.As researchers continue to follow patients from the COMET trial, they hope to learn more about how invasive breast cancers behave over time. Finally, Dr. Thorat encourages clinicians and scientists to rethink breast cancer treatment and develop better ways to identify which patients truly need surgery—and which do not.DOI - https://doi.org/10.18632/oncotarget.28698Correspondence to - Mangesh A. Thorat - m.thorat@qmul.ac.ukTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
What if a cancer treatment worked—until it suddenly didn’t? A new case report, “Acquired RUFY1-RET rearrangement as a mechanism of resistance to lorlatinib in a patient with CD74-ROS1 rearranged non-small cell lung cancer: A case report,” published in Oncotarget, reveals how a non-small cell lung cancer (NSCLC) patient developed drug resistance through a rare genetic alteration, allowing the cancer to evade therapy. This unexpected finding highlights the importance of advanced genetic testing and personalized cancer treatments.Non-Small Cell Lung Cancer, Targeted Therapy and Drug ResistanceNon-Small Cell Lung Cancer is the most common type of lung cancer, accounting for nearly 85% of all cases. Some patients with NSCLC have genetic mutations, such as ROS1 gene fusions, that drive tumor growth. These patients often respond well to targeted therapies like lorlatinib, a ROS1 inhibitor that blocks cancer growth.However, cancer is constantly evolving. Over time, it can develop resistance to targeted therapies, leading to treatment failure. Understanding these resistance mechanisms is crucial for precision oncology, the approach of tailoring cancer treatment based on a patient’s unique genetic profile.Full. blog - https://www.oncotarget.org/2025/03/12/a-rare-genetic-shift-that-helped-lung-cancer-evade-treatment/DOI - https://doi.org/10.18632/oncotarget.28682Correspondence to - Wade T. Iams - wade.t.iams@vumc.orgVideo short - https://www.youtube.com/watch?v=HE_qSkcRZhoAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - March 11, 2025 – A new #editorial was #published in Oncotarget, Volume 16, on March 10, 2025, titled “EXPOSOMES and GENES: The duo influencing CANCER initiation and progression."In this editorial, Drs. Uzma Saqib, Katherine E. Ricks, Alexander G. Obukhov, and Krishnan Hajela from Devi Ahilya Vishwavidyalaya (DAVV) in Indore, India, discuss how environmental factors, known as exposomes, interact with genes to influence cancer risk. The authors highlight how pollution, diet, infections, and chronic stress can trigger genetic alterations that may lead to cancer. Understanding these connections could play a crucial role in cancer prevention and public health strategies.Genes store the instructions for how the body functions, but they can be damaged by harmful exposures. Polluted air, radiation, tobacco smoke, and processed foods can lead to DNA damage, interfering with the body’s natural ability to repair itself. Over time, these genetic changes can increase the risk of cancer development. The authors emphasize that nearly everyone is exposed to cancer risk factors daily. “According to the Global Air Quality Guidelines of World Health Organization (WHO), nearly all of the global population (>99%) breathes polluted air that exceeds guideline limits.”For example, air pollution has been linked to lung cancer, while UV radiation is a leading cause of skin cancer. Processed meats contain harmful chemicals that can damage DNA, and excessive alcohol consumption has been shown to raise the risk of liver cancer by causing toxic buildup in cells. Even chronic stress and hormone imbalances can weaken the body’s natural defenses against cancer by altering key genetic pathways.Infections also play a critical role in cancer risk. The Helicobacter pylori bacterium can cause stomach cancer by damaging stomach cells, while human papillomavirus (HPV) is strongly linked to cervical cancer. Other bacteria, viruses, and fungi can introduce genetic instability that contributes to tumor growth.Despite these risks, scientists estimate that up to 40% of cancers could be prevented through lifestyle changes such as a healthy diet, regular exercise, and avoiding harmful exposures. Advances in research technology are helping scientists better understand how environmental factors alter genes, leading to new strategies for cancer detection and prevention.“Understanding the exposome-gene-cancer research axis will have a significant impact on public health and the development of more effective strategies for prevention and treatment of diseases.”The editorial underscores the urgent need for greater public awareness and policy action to reduce exposure to harmful environmental risks. As scientists continue to explore the connection between exposomes and genetic changes, their findings could revolutionize public health efforts and cancer prevention strategies.By recognizing the long-term impact of environmental exposures, individuals, communities, and policymakers can take meaningful steps toward reducing cancer risk and promoting healthier environments for future generations.DOI - https://doi.org/10.18632/oncotarget.28696Correspondence to - Krishnan Hajela - hajelak@gmail.comVideo short - https://www.youtube.com/watch?v=kE4XX9ULHBQTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - March 3, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on February 28, 2025, titled “Effect of TIMPs and their minimally engineered variants in blocking invasion and migration of brain cancer cells."Elham Taheri and Maryam Raeeszadeh-Sarmazdeh from the University of Nevada, Reno, explored a new approach to slowing the spread of glioblastoma multiforme (GBM), the most aggressive and deadly form of brain cancer. Their study highlights the potential of both natural and engineered molecules to block cancer cell movement, offering a promising strategy to combat this challenging disease.Glioblastoma multiforme is difficult to treat because it quickly spreads into healthy brain tissue, making complete surgical removal nearly impossible. A major driver of this invasive behavior is a group of enzymes called matrix metalloproteinases (MMPs), which break down surrounding tissue and create space for cancer cells to spread. Among them, MMP-9 plays a particularly significant role in GBM progression and resistance to current treatments.To address this challenge, the researchers investigated tissue inhibitors of metalloproteinases (TIMPs), natural MMP blockers, and specially engineered versions designed for better effectiveness. The study used cell line models of GBM to test both TIMP-1 and TIMP-3 and their engineered counterparts (mTC1 and mTC3), specific blockers of MMP-9. “Our study focused on minimal TIMP variants, due to their small molecular size and potential in higher cellular uptake and delivery, to assess their potential in cell-based assays.”The results indicated that the engineered TIMPs were just as effective as, or even better than, the natural ones at reducing cancer cell migration and invasion. These findings are particularly promising because previous attempts to block MMPs with small-molecule drugs faced challenges such as poor selectivity and unwanted side effects. In contrast, these engineered TIMPs offer a more targeted and potentially safer approach.One of the greatest obstacles in treating brain cancer is delivering drugs across the blood-brain barrier, a protective layer that prevents many therapeutic compounds from reaching the brain. To address this, the researchers used cell-penetrating peptides to help the TIMP variants reach and enter cancer cells more effectively. Their results confirmed that the engineered TIMPs successfully reached tumor cells, further increasing their potential as a treatment.Additionally, the study found that these engineered TIMPs did not significantly affect healthy cells at lower doses, suggesting they could be used safely. This makes them strong candidates for further drug development.These findings could lead to new treatment options for GBM, a cancer with very few effective therapies. Future research will focus on testing these TIMP variants in animal models to evaluate their long-term effects and safety. Researchers also plan to investigate whether combining these engineered TIMPs with existing treatments, such as chemotherapy or immunotherapy, could improve outcomes.In summary, given the aggressive nature of GBM and the urgent need for better therapies, this study represents an important step forward. If further research confirms these results, engineered TIMPs could become a valuable tool in the fight against brain cancer, offering new hope for improved treatments and patient survival.DOI - https://doi.org/10.18632/oncotarget.28691Correspondence to - Maryam Raeeszadeh-Sarmazdeh - maryamr@unr.eduVideo short - https://www.youtube.com/watch?v=tdBlkOX50D8To learn more about Oncotarget, please visit https://www.oncotarget.com.MEDIA@IMPACTJOURNALS.COM
Imagine if a single blood test could tell clinicians in real time how successful a cancer surgery has been. A recent study from the University of Brasília, published in Oncotarget, suggests that such an approach might soon be possible. By tracking changes in cell-free DNA (cfDNA) levels before, during, and after colorectal cancer (CRC) surgery, researchers have found a potential new way to monitor tumor removal and predict patient outcomes.Cell-Free DNA and Colorectal Cancer SurgeryCell-free DNA consists of tiny fragments of genetic material that are released into the bloodstream when cells break down. In healthy individuals, these fragments come from normal cell turnover, but in cancer patients, some of this DNA originates from tumor cells. cfDNA detection has been used to track cancer progression and treatment response in diseases like lung, breast, and CRC. What had not been investigated until now was how cfDNA levels fluctuate during cancer surgery itself.Since surgery is the primary treatment for CRC, understanding how cfDNA levels change during surgical intervention could provide valuable insights into whether the tumor has been fully removed and how the patient’s body reacts to the procedure.The Study: Measuring Cell-Free DNA in Real-TimeIn the study, titled “Assessment of cfDNA release dynamics during colorectal cancer surgery,” led by first author Mailson Alves Lopes and corresponding author Fabio Pittella-Silva, scientists analyzed blood plasma samples from 30 CRC patients at three critical time points—before, during, and after surgery. Using highly sensitive genetic tests, they measured changes in cfDNA concentration to determine whether surgery had a direct impact on its release. The goal was to check whether cfDNA could serve as a biomarker for evaluating surgical effectiveness and predicting the probability of cancer recurrence.Full blog - https://www.oncotarget.org/2025/02/26/how-a-simple-blood-test-could-predict-colorectal-cancer-surgery-success/Paper DOI - https://doi.org/10.18632/oncotarget.28681Correspondence to - Fabio Pittella-Silva - pittella@unb.brVideo short - https://www.youtube.com/watch?v=jC5_xqIrbtASign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28681Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, colorectal cancer, cfDNA, surgeryAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - February 24, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on February 18, 2025, titled “Robust p53 phenotypes and prospective downstream targets in telomerase-immortalized human cells."Researchers Jessica J. Miciak, Lucy Petrova, Rhythm Sajwan, Aditya Pandya, Mikayla Deckard, Andrew J. Munoz, and Fred Bunz from the Sidney Kimmel Comprehensive Cancer Center and Johns Hopkins University School of Medicine studied the tumor-suppressing protein p53, which plays a key role in preventing cancer. Their findings reveal how p53 affects cancer cell growth, treatment resistance, and potential drug targets, providing new insights that could improve future cancer therapies.The p53 protein plays a crucial role in preventing cancer by stopping uncontrolled cell growth. However, many cancers mutate or suppress p53, allowing tumors to develop and resist treatment. In this study, researchers restored p53 function in colorectal cancer cells, which led to slower cellular growth, increased cellular aging (senescence), and greater sensitivity to radiation therapy. These findings suggest that p53 status influences cancer progression and response to treatment, making it a promising target for new therapies.The study also examined hTERT-RPE1 cells; a type of non-cancerous human cell used in research. When the TP53 gene was disrupted in these cells, they grew faster and became more resistant to radiation, reinforcing the idea that p53 helps prevent cancerous growth.Another key discovery was a previously unnoticed p53 mutation (A276P) found in a subset of hTERT-RPE1 cells. This mutation weakened p53’s ability to regulate certain genes but did not affect its ability to control calcium signaling, a process important for cell survival. The unexpected appearance of this mutation suggests that even non-cancerous cells can acquire genetic changes that mimic early cancer development. This insight could help scientists better understand how cancers evolve and become resistant to treatment."Cancers that retain wild type TP53 presumably harbor other clonal alterations that permitted their precursors to bypass p53-mediated growth suppression."A breakthrough in the study was the identification of two new p53-regulated genes that could be important for cancer treatment. The first, ALDH3A1, helps detoxify harmful substances and may impact cancer cell resistance to oxidative stress. The second, NECTIN4, is a protein found in many aggressive cancers, including bladder and breast cancer. Notably, NECTIN4 is the target of enfortumab vedotin, an FDA-approved drug for bladder cancer. These discoveries provide new potential drug targets and could lead to improved therapies for cancers that still retain some p53 function.In conclusion, this research highlights the critical role of p53 in cancer biology and suggests that restoring p53 function could make tumors more vulnerable to radiation and chemotherapy. The discovery of new p53-controlled genes provides new opportunities for targeted cancer therapies. With further research, these findings could lead to new precision medicine strategies that leverage p53’s natural tumor-suppressing abilities.DOI - https://doi.org/10.18632/oncotarget.28690Correspondence to - Fred Bunz - fredbunz@jhmi.eduVideo short - https://www.youtube.com/watch?v=Psxj3ctbTukTo learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - February 25, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on February 18, 2025, titled “Leukopenia, weight loss and oral mucositis induced by 5-Fluorouracil in hamsters’ model: A regenerative approach using electrospun poly(Lactic-co-Glycolic Acid) membrane."Researchers from the Federal University of Rio de Janeiro and Brazilian Center for Research in Physics have investigated a novel approach to treating oral mucositis, a painful and debilitating side effect of chemotherapy. Led by first author and corresponding author Ana Chor, the study examined the effectiveness of an electrospun poly (Lactic-co-Glycolic Acid) (PLGA) membrane in promoting tissue regeneration in an animal model of chemotherapy-induced oral mucositis. The findings suggest that PLGA membranes, particularly when combined with the body's own healing cells, significantly accelerate the recovery process and reduce inflammation. This promising discovery could lead the way for improved treatments for cancer patients experiencing severe mouth ulcers during chemotherapy.Oral mucositis affects many cancer patients undergoing 5-Fluorouracil (5-FU) chemotherapy, often leading to difficulty in eating, drinking, and speaking. Despite its prevalence, effective treatments remain limited. In this study, researchers applied electrospun PLGA membranes to 5-FU-induced ulcers in hamsters. Some of these membranes were infused with autologous mesenchymal cells—cells taken from the animal itself—to enhance the healing process.The study showed significant results, as ulcers treated with PLGA membranes containing autologous cells healed completely within six days, along with reduced inflammation and the formation of new blood vessels essential for tissue repair. While PLGA membranes without added cells also contributed to healing, the recovery process was slower."This innovative approach holds significant therapeutic potential, as it utilizes the host’s mesenchymal cells and nanotechnology tools to design a scaffold that mimics the organism’s microenvironment."These findings highlight the potential of using bioengineered materials to treat chemotherapy-induced oral lesions. While further research is necessary before this approach can be tested in clinical settings, the study provides a strong foundation for future investigations. If successfully translated to human treatment, this technique could significantly improve the quality of life for cancer patients by offering a more effective solution for managing chemotherapy-related mouth ulcers.DOI - https://doi.org/10.18632/oncotarget.28685Correspondence to - Ana Chor - anamedoral@gmail.comVideo short - https://www.youtube.com/watch?v=0hGgRAlcBQASubscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - February 18, 2025 – A new #researchpaper was #published in Oncotarget, Volume 16, on February 12, 2025, titled “Could Panitumumab with very low dose Capecitabine be an option as a maintenance regimen."In this study, researchers Doaa A. Gamal, Aiat Morsy, and Mervat Omar from Assiut University Hospital, evaluated a new maintenance treatment for metastatic colorectal cancer (mCRC). Their findings suggest that a combination of two drugs—Panitumumab, a targeted therapy that blocks a protein called epidermal growth factor receptor to slow cancer growth, and low-dose Capecitabine, a chemotherapy drug that converts into 5-fluorouracil (5-FU) inside the body to stop cancer cells from growing and dividing—could help extend survival in patients with mCRC. This regimen appears to be both effective and well-tolerated, especially for patients with wild-type KRAS mCRC who had previously responded to treatment.Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. Standard treatment often involves a combination of chemotherapy and targeted therapies, but many patients face challenges related to treatment toxicity and resistance, which can lead to treatment interruptions. This study tested whether a lower-intensity maintenance treatment could help keep the cancer under control after initial treatment.The study involved 25 mCRC patients with wild-type KRAS and BRAF, who first received six rounds of standard 5-FU-based chemotherapy with Panitumumab. Patients who responded well then switched to a maintenance treatment of Panitumumab every two weeks and a low, continuous dose of Capecitabine. The results showed that patients had a median progression-free survival of 18 months and a median overall survival of 45 months, indicating a strong potential benefit.Patients with metastases detected at the same time as the primary tumor showed a longer progression-free survival than those with metastases appearing later. The treatment was also well tolerated, with only 8% of patients experiencing severe side effects such as skin rash or diarrhea, which were managed with standard treatments."In our research, the toxicity profile was very acceptable, and no patients needed to stop treatment or had a dose modification due to toxicity."Finding a way to keep cancer under control while reducing side effects is a major goal in cancer treatment. While other maintenance therapies like Bevacizumab and Cetuximab have been studied, this research suggests that Panitumumab with low-dose Capecitabine could be a promising new option. Panitumumab is already an FDA-approved drug, but its role in maintenance therapy had not been extensively explored. The results of this study suggest that this combination may help delay disease progression while keeping side effects manageable, ultimately improving patients’ quality of life.Although larger studies are needed, these findings open the door for further clinical trials to confirm the benefits of this regimen. If validated, this approach could change the standard of care for mCRC patients, particularly those who cannot tolerate more intensive chemotherapy.DOI - https://doi.org/10.18632/oncotarget.28687Correspondence to - Doaa A. Gamal - doaaalygamaal@gmail.comVideo short - https://www.youtube.com/watch?v=wuPSS0EdK-8To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY – February 14, 2025 – A new #review was #published in Oncotarget, Volume 16, on February 12, 2025, titled “SETDB1 amplification in osteosarcomas: Insights from its role in healthy tissues and other cancer types.”Authors Elodie Verdier, Nathalie Gaspar, Maria Eugenia Marques Da Costa, and Antonin Marchais from the Gustave Roussy Cancer Campus analyzed recent studies on a gene called SETDB1, which may play a key role in osteosarcoma, a type of bone cancer that mostly affects teenagers and young adults. Their review highlights how SETDB1 helps cancer cells grow, resist treatment, and avoid the immune system. Because of this, blocking SETDB1 could be a promising new way to treat osteosarcoma.Osteosarcoma is a fast-growing bone cancer that is usually treated with surgery and chemotherapy. However, if the cancer spreads or returns, treatment options are very limited. Scientists are searching for new ways to stop this disease, and recent studies have found that osteosarcoma cells often have extra copies of the SETDB1 gene. This seems to make the cancer more aggressive and harder to treat.“Whole exome sequencing of osteosarcoma samples from both diagnosis and relapses has highlighted several factors, including SETDB1, that are amplified in the most aggressive forms of the disease.”SETDB1 is involved in epigenetics, meaning it affects how genes are turned on and off without changing the DNA itself. The review explains that SETDB1 helps tumors hide from the immune system, making it difficult for the body to fight the cancer naturally. The researchers believe that blocking SETDB1 could help the immune system recognize and attack osteosarcoma cells. Some experimental drugs that target SETDB1 are already being tested in the lab.The review also describes how SETDB1 influences key cancer pathways, such as Wnt signaling, which helps cancer cells grow, and epithelial-mesenchymal transition (EMT), a process that allows cancer to spread. The authors suggest that combining SETDB1-blocking drugs with immunotherapy or radiation could be an effective new strategy for treating osteosarcoma.Another key finding is that SETDB1 may help cancer cells become resistant to chemotherapy, making treatment less effective. This means that drugs targeting SETDB1 could not only slow cancer growth but also make existing treatments work better.While more research is needed, this review brings attention to SETDB1 as a potential treatment target. Scientists hope that a deeper understanding of SETDB1 will lead to new therapies that improve survival rates for osteosarcoma patients.DOI - https://doi.org/10.18632/oncotarget.28688Correspondence to - Antonin Marchais - antonin.marchais@gustaveroussy.fr, and Maria Eugenia Marques Da Costa - jenny.marquescosta@gustaveroussy.frVideo short - https://www.youtube.com/watch?v=f9WgaDoEubsAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
For years, breast cancer has been classified as either HER2-positive or HER2-negative, determining whether a patient could receive HER2-targeted therapies like trastuzumab (Herceptin). However, a growing body of research suggests a middle category—HER2-low breast cancer—which has led to important changes in how clinicians approach treatment.A recent review published in Oncotarget, titled “Evolving Concepts in HER2-Low Breast Cancer: Genomic Insights, Definitions, and Treatment Paradigms,” explores what this means for both patients and clinicians.Full blog - https://www.oncotarget.org/2025/02/12/her2-low-breast-cancer-a-new-understanding/Paper DOI - https://doi.org/10.18632/oncotarget.28680Correspondence to - Andrew A. Davis - aadavis@wustl.eduVideo short - https://www.youtube.com/watch?v=dn54UrHCUNQSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28680Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, breast cancer, HER2-low, genomicsAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - February 10, 2025 – A new #casereport was #published in Volume 16 of Oncotarget on February 5, 2025, titled “A case report of donor cell–derived hematologic neoplasms 9 years after allogeneic hematopoietic cell transplantation."In this case report, Aleksandra Mroczkowska-Bękarciak and Tomasz Wróbel from Wroclaw Medical University describe a rare and serious complication after a stem cell transplant. The case involves a patient who, nine years after receiving a stem cell transplant for acute myeloid leukemia (AML), developed a new, aggressive blood cancer originating from donor cells. Despite receiving treatment, the disease progressed to myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), ultimately leading to the patient’s death.Stem cell transplants are a life-saving treatment for many blood cancers, including AML. While relapse of the original cancer is the most common concern, this case highlights another rare but serious complication: the development of donor cell-derived hematologic neoplasms (DCHN).The report details the case of a 23-year-old woman who remained in remission for nearly 10 years following a successful hematopoietic stem cell transplant from an unrelated donor. However, she later developed a new form of leukemia, driven by genetic mutations in the ASXL1, SETBP1, and EZH2 genes—biomarkers linked to highly aggressive blood cancers. Over the next two years, the disease progressed despite intensive treatment, ultimately proving fatal.This case highlights the need for continued monitoring of transplant recipients, even years after the procedure. Although DCHN is extremely rare, its occurrence raises critical questions about the process by which donor cells transform into leukemia.Some stem cell donors may unknowingly carry genetic mutations that are harmless in their own bodies but could trigger cancer in recipients. Additionally, factors such as immunosuppressive therapy, bone marrow stress, and transplantation procedures may contribute to these rare but deadly outcomes.“Early diagnosis and intervention are crucial to improving patient prognosis.” Ongoing research is focused on improving donor screening methods to help predict and prevent these complications. In the future, routine genetic testing for stem cell donors could become a standard part of the transplant process, helping clinicians identify potential risks before transplantation.More studies are needed to fully understand why donor-derived cancers develop and how they can be prevented. With continued progress in precision medicine and genetic diagnostics, researchers aim to make stem cell transplants safer and more effective for all patients.DOI - https://doi.org/10.18632/oncotarget.28686Correspondence to - Aleksandra Mroczkowska-Bękarciak - omroczkowska@interia.plVideo short - https://www.youtube.com/watch?v=G2zd0UqWzeEAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - February 6, 2025 – A new #casereport was #published in Volume 16 of Oncotarget on February 5, 2025, titled “Acquired RUFY1-RET rearrangement as a mechanism of resistance to lorlatinib in a patient with CD74-ROS1 rearranged non-small cell lung cancer: A case report."In this case report, Jenny L. Wu from Vanderbilt University School of Medicine and Wade T. Iams from Vanderbilt-Ingram Cancer Center describe a rare case of drug resistance in a patient with advanced non-small cell lung cancer (NSCLC). The patient, a 42-year-old man who had never smoked, initially responded well to lorlatinib, a targeted therapy designed to treat cancer driven by specific genetic alterations. However, after six months, his cancer began to grow again. Clinicians discovered that this was due to a new genetic change, known as the RUFY1-RET fusion. This finding highlights how cancers can adapt to treatment and the importance of ongoing genetic testing to guide therapy decisions.NSCLC is the most common type of lung cancer, and in some cases, it is driven by genetic changes that can be targeted with specific drugs. The patient’s cancer originally had a ROS1 gene rearrangement, which made it responsive to lorlatinib. But as time went on, the cancer started to grow again, and tests revealed a new genetic alteration called RUFY1-RET fusion, which likely caused resistance to lorlatinib.This new genetic change was identified using RNA next-generation sequencing (RNA NGS), an advanced test that can find mutations that standard genetic tests might miss. After discovering the RUFY1-RET gene fusion, the patient was treated with a combination of lorlatinib and pralsetinib, a drug that specifically targets RET gene alterations. While this combination helped control the cancer for about four months, the patient’s condition unfortunately worsened after four months.“This is the first reported case of a RET fusion as a potential mechanism of resistance to lorlatinib, it identifies a novel RET fusion partner, and it emphasizes the importance of testing for acquired resistance mutations with both DNA and RNA at the time of progression in patients with targetable oncogenic drivers.”Understanding cases like this can help clinicians and researchers develop more effective treatment strategies, including combination therapies that target multiple genetic changes to combat drug resistance. While the combined therapy in this case provided only temporary benefits, it offers important insights for future research and patient care, particularly for cancers that no longer respond to standard treatments.DOI: https://doi.org/10.18632/oncotarget.28682Correspondence to: Wade T. Iams, wade.t.iams@vumc.orgKeywords: cancer, ROS1 rearrangement, RET rearrangement, non-small cell lung cancer, targeted therapy, case reportSubscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
An unexpected link between KLRG1 and PD-1, two key immune system proteins, was revealed in a study recently published in Oncotarget. This discovery could help explain why some cancer immunotherapy treatments are less effective for certain patients and lead to new therapeutic strategies.How the Immune System Fights CancerThe immune system is a powerful defense mechanism against cancer, with CD8 T cells acting as the primary soldiers. These specialized immune cells identify and destroy tumor cells. However, cancer can cleverly evade this attack by manipulating immune checkpoints—natural “breaks” on the immune system that prevent it from overreacting and damaging healthy tissue.One of the most studied checkpoints is PD-1 (Programmed Death-1), a receptor on T cells that acts as an “off switch” when activated by tumor cells. This mechanism suppresses the immune response, allowing cancer to grow without control. In response, researchers have developed treatments called PD-1 inhibitors, which block this “off switch” and keep T cells active. The Study: Investigating KLRG1 and PD-1 in Tumor-Fighting T CellsIn the study titled “Anti-correlation of KLRG1 and PD-1 expression in human tumor CD8 T cells,” Dr. Steven A. Greenberg from Harvard Medical School analyzed publicly available gene expression data from various cancer types, including lung cancer, melanoma, and colorectal cancer. His goal was to identify immune-related proteins that could complement existing therapies, such as PD-1 inhibitors.Full blog - https://www.oncotarget.org/2025/01/28/a-new-approach-for-cancer-treatment-the-surprising-relationship-between-klrg1-and-pd-1/Paper DOI - https://doi.org/10.18632/oncotarget.28679Correspondence to - Steven A. Greenberg - sagreenberg@bwh.harvard.eduVideo short - https://www.youtube.com/watch?v=PME2xfyYN18Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28679Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, immunotherapy, KLRG1About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - January 27, 2025 – A new #research paper was #published in Oncotarget's Volume 16 on January 21, 2025, titled “Assessment of cfDNA release dynamics during colorectal cancer surgery."Researchers from the University of Brasília investigated how cell-free DNA (cfDNA) levels in the blood change before, during, and after colorectal cancer surgery. The study found that cfDNA levels increase significantly during and after surgery. The findings suggest that cfDNA could help clinicians evaluate surgery effectiveness and monitor patient outcomes.cfDNA consists of small DNA fragments released into the bloodstream when cells die and break apart. In healthy individuals, cfDNA usually comes from normal cell turnover, while in cancer patients, some of it originates from tumor cells. Measuring cfDNA levels offers valuable insights into a patient’s condition and is already being used to track disease progression and treatment response in cancers such as lung, breast, and colorectal cancer.Colorectal cancer is one of the most common cancers worldwide, affecting millions of people each year. Surgery is often the primary treatment, but up to 50% of patients experience cancer recurrence afterward. In this study, the research team, led by first author Mailson Alves Lopes and corresponding author Fabio Pittella-Silva, analyzed blood samples from 30 patients at three key time points: before, during, and after surgery.It was found that cfDNA levels increased nearly threefold during surgery and doubled after surgery compared to pre-surgery levels. The increases were even higher in individuals over 60, those with preexisting conditions such as diabetes or heart disease, and patients with elevated levels of carcinoembryonic antigen (CEA), a common cancer marker. Patients with the highest cfDNA levels were those with larger or more aggressive tumors, likely due to greater tissue damage during surgery. Additionally, longer surgeries were linked to higher cfDNA levels.“[...]we observed that cfDNA concentration may rise in correlation with the duration of the surgery, highlighting its potential as a marker of surgical quality.”These findings suggest that cfDNA could be a valuable, non-invasive biomarker for clinicians to monitor colorectal cancer patients. Tracking cfDNA levels may help better evaluate surgical outcomes and determine whether patients require closer follow-up care. While these findings are promising, further research is needed to standardize cfDNA testing and validate its usefulness. Larger studies could help establish cfDNA testing as a reliable tool for cancer care and postoperative monitoring, with the potential to become a routine part of clinical practice in the future.DOI - https://doi.org/10.18632/oncotarget.28681Correspondence to - Fabio Pittella-Silva - pittella@unb.brVideo short - https://www.youtube.com/watch?v=jC5_xqIrbtAAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - January 22, 2025 – A new #review was #published in Oncotarget's Volume 16 on January 20, 2025, titled “Evolving concepts in HER2-low breast cancer: Genomic insights,definitions, and treatment paradigms."Researchers Whitney L. Hensing, Emily L. Podany, James J. Sears, Shaili Tapiavala, and Andrew A. Davis from the University of Missouri-KC School of Medicine and Washington University in St. Louis School of Medicine explore HER2-low breast cancer, a recently recognized type of breast cancer that is changing the way clinicians should approach treatment. The review explains what makes HER2-low breast cancer different and highlights new treatment options that are helping patients.“Breast cancer, which has been historically classified as HER2-positive versus HER2-negative, is currently facing a paradigm shift in both the definition of HER2 status and in the existing treatment algorithms.”Breast cancer is usually classified into two main types based on the HER2 protein: HER2-positive or HER2-negative. HER2-low breast cancer falls somewhere in between. Thanks to new targeted treatments, such as a drug called trastuzumab deruxtecan, patients with HER2-low breast cancer now have more options and better chances of responding to treatment.The review looks at recent studies on the genetics of HER2-low breast cancer. Researchers found that these tumors are often hormone receptor (HR)-positive, meaning they respond to hormones like estrogen. Some tumors also carry a common genetic change called a PIK3CA mutation, which could affect how well treatments work. However, experts say HER2-low breast cancer is not a completely separate breast cancer type but rather an opportunity for more personalized treatment.“Despite evidence from existing literature that HER2-low breast cancer does not represent a distinct biologic and prognostic subtype, the introduction of HER2-low expression as a therapeutic target has expanded patient eligibility for a potent class of anti-HER2 drugs, HER2-directed ADCs, with potential for significant efficacy.”Despite these advances, diagnosing HER2-low breast cancer can still be difficult. Current testing methods are not always accurate, and different laboratories may get different results. The review calls for better detection methods to make sure patients who can benefit from these new treatments are correctly identified.With cancer treatments becoming more personalized, the review also explains how clinicians can fit HER2-low treatments into existing guidelines to help patients. The success of targeted therapies is changing how breast cancer is treated, especially for patients whose cancer has metastasized.In conclusion, experts believe ongoing research will continue to improve the way HER2-low breast cancer is diagnosed and treated. However, they stress the need for better detection methods and continued exploration of new therapies to help patients get the best possible care.DOI - https://doi.org/10.18632/oncotarget.28680Correspondence to - Andrew A. Davis - aadavis@wustl.eduAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - January 21, 2025 – A new #research paper was #published in Oncotarget's Volume 16 on January 20, 2025, titled “Anti-correlation of KLRG1 and PD-1 expression in human tumor CD8 T cells."The study, authored by Dr. Steven A. Greenberg from Harvard Medical School, has discovered a potential new way to improve cancer treatment by studying two key molecules found in immune cells: KLRG1 and PD-1. Analysis of data from cancer patients and healthy individuals revealed that these molecules work in opposite ways in cancer-fighting cells, suggesting that targeting both at the same time could enhance the effectiveness of cancer immunotherapy.“Much effort in the field of immuno-oncology has involved the study of combination therapies, including combinations involving blockade of more than one T cell inhibitory receptor.”The immune system helps fight cancer through specialized cells called T cells. Treatments known as checkpoint inhibitors, which block proteins like PD-1, have been successful in helping these cells attack cancer. However, combining different checkpoint inhibitors has not always provided the expected improvements. This new research focuses on KLRG1, a lesser-known protein, and its relationship with PD-1. The findings suggest that targeting both markers simultaneously could create a stronger and more effective immune response against cancer. Most existing immunotherapy treatments focus only on blocking PD-1, which is commonly found in “exhausted” T cells that struggle to fight cancer. In contrast, KLRG1 is linked to more active, mature T cells that are better at attacking tumors. By blocking both PD-1 and KLRG1, new treatment strategies could help patients with hard-to-treat cancers, such as lung cancer, melanoma, and colorectal cancer.KLRG1 has not been widely studied in cancer immunotherapy, but this research highlights its potential to revolutionize treatment strategies. While current combinations of checkpoint inhibitors have shown only limited improvements, using therapies that target both PD-1 and KLRG1 could lead to more significant and long-lasting benefits.“Whereas much of the T cell inhibitory drug development efforts over the last decade have been focused on combinations of expression-correlated inhibitory receptor targets, the targeting of anti-correlated inhibitory receptors has greater potential to produce supra-additive benefit, and KLRG1 has this distinct property.”Further studies and clinical trials are needed to explore how combining PD-1 and KLRG1 treatments could benefit different types of cancer. If successful, this strategy could open the door for the creation of new combined immunotherapies.DOI - https://doi.org/10.18632/oncotarget.28679Correspondence to - Steven A. Greenberg - sagreenberg@bwh.harvard.eduVideo short - https://www.youtube.com/watch?v=PME2xfyYN18About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
Scientists have discovered that a genetic variant called KIT M541L may play an important role in a rare immune disorder known as #mastocytosis. The findings may help explain why some #patients develop more severe forms of the disease.Understanding MastocytosisMastocytosis is a condition where the body produces too many mast cells. These cells are part of the immune system and help the body fight infections, but in excess, they release chemicals that can cause itching, swelling, and even serious organ damage.There are two main types of mastocytosis. The first is cutaneous mastocytosis, which mostly affects the skin. The second is systemic mastocytosis, a more serious form where mast cells build up in internal organs like the liver, spleen, and bone marrow.The disease is linked to mutations in the KIT gene, which regulates mast cell growth. The most studied mutation is KIT D816V, but recent research has highlighted another variant, KIT M541L.The Study: Impact of KIT M541L VariantA team of researchers at the National Institutes of Health (NIH), led by first author Luisa N. Dominguez Aldama and corresponding author Melody C. Carter, aimed to better understand the prevalence and impact of the KIT M541L genetic variant in mastocytosis patients. The study published in Oncotarget on July 22, 2024, titled “Prevalence and impact of the KIT M541L variant in patients with mastocytosis,” examined the presence of the KIT M541L gene variant in 100 patients with mastocytosis, both adults and children, alongside 500 healthy individuals. By comparing these two groups, the researchers wanted to see if there was a relation between the KIT M541L variant and mastocytosis severity.Full blog - https://www.oncotarget.org/2025/01/15/mastocytosis-key-insights-into-kit-m541l-gene-mutation/Paper DOI - https://doi.org/10.18632/oncotarget.28614Correspondence to - Melody C. Carter - mcarter@niaid.nih.govVideo short - https://www.youtube.com/watch?v=zpiBbSfkTX4Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28614Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, mastocytosis, KIT M541L, KIT D816V, adults, pediatricsAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
Would you take a test to find out your cancer risk? At-home genetic testing makes it easy, but experts warn that these tests may create more harm than good.A New Approach to Genetic TestingGenetic testing has traditionally been performed under the supervision of healthcare providers, with genetic counseling to help patients navigate their results. This approach ensures that individuals receive proper guidance, reducing the emotional and practical challenges of interpreting complex genetic information.In September 2023, the United States Food and Drug Administration (FDA) approved a new test called the Invitae Common Hereditary Cancers Panel. This test checks for changes in 48 genes linked to hereditary cancers, including breast, ovarian, and Lynch syndrome-related cancers. What makes it different is that it can be ordered online and taken at home with no doctor required.While the convenience of these tests is appealing, health experts have raised serious concerns. An editorial titled “Pitfalls and Perils from FDA-Approved Germ-line Cancer Predisposition Tests,” authored by Dr. Wafik S. El-Deiry, Editor-in-Chief of Oncotarget, and Dr. Eli Y. Adashi, both from Brown University, highlights the potential risks of using these tests without professional guidance.Full blog - https://www.oncotarget.org/2025/01/03/the-hidden-risks-of-at-home-genetic-cancer-tests/Paper DOI - https://doi.org/10.18632/oncotarget.28677Correspondence to - Wafik S. El-Deiry - wafik@brown.eduVideo short - https://www.youtube.com/watch?v=DjKpiBNDWHoSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28677Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, cancer predisposition, germline, marketing authorization, hereditary cancer, direct to consumerAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - December 30, 2024 – A new #editorial was #published in Oncotarget's Volume 15 on December 24, 2024, titled “Pitfalls and perils from FDA-approved germ-line cancer predisposition tests."Authored by Dr. Wafik S. El-Deiry, Editor-in-Chief of Oncotarget, and Dr. Eli Y. Adashi from Brown University, the article highlights concerns about the risks of a newly approved genetic test for cancer risk. This test, called the “Invitae Common Hereditary Cancers Panel," was approved in 2023 and examines 48 genes linked to inherited cancers, including breast, ovarian, and Lynch syndrome-related cancers. Although the test increases access to genetic information, the authors warn that using it without professional guidance may lead to confusion, stress, and potential harm.One concern is that people can order this test online without consulting healthcare professionals or genetic counselors. Without expert help, users might struggle to understand their results especially if they indicate risks that are unclear or difficult to act on. This can cause unnecessary anxiety and confusion.“The DTC option of germ-line testing for cancer susceptibility should be discouraged given the risks of anxiety, lack of adequate interpretation for variants not strongly associated with cancer, potential for minors to be tested outside the healthcare system and potential for loss of follow-up if test results are not shared with health care professionals or never make it into the medical record.”The editorial also points out ethical and medical issues when minors use these tests. If a child’s test is done without medical oversight, results might not be added to their health records, making follow-up care harder to manage and potentially risking their long-term health.Cost is another issue. These tests are often not covered by insurance, which can place a financial burden on families who might need additional testing or medical advice.The researchers emphasize that genetic testing for cancer risk should always include healthcare providers and genetic counseling. This ensures users fully understand their results and receive proper guidance. The authors also call on the US Food and Drug Administration (FDA) to provide clear rules for using these tests, particularly for minors.In conclusion, while genetic testing holds great potential for improving cancer prevention and care, its benefits must not come at the cost of safety and public health. Responsible use of these tests will require collaboration between regulators, healthcare professionals, and testing companies to address the risks and ensure these tools are used effectively.DOI - https://doi.org/10.18632/oncotarget.28677Correspondence to - Wafik S. El-Deiry - wafik@brown.eduVideo short - https://www.youtube.com/watch?v=DjKpiBNDWHoSubscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
The p53 protein, often called the “guardian of the genome,” is crucial for preventing cancer by repairing damaged DNA or triggering cell death in cells that cannot be repaired. However, in about half of all cancers, the p53 gene is mutated, making the protein ineffective. A groundbreaking study has introduced PG3, a new compound that restores tumor suppression without relying on p53, offering a new option to treat resistant cancers.Published in Oncotarget on September 17, 2024, the study titled “Integrated stress response (ISR) activation and apoptosis through HRI kinase by PG3 and other p53 pathway-restoring cancer therapeutics,” introduces PG3, a small molecule with a completely new approach to treating cancer. This groundbreaking research was conducted by Dr. Xiaobing Tian and Oncotarget Editor-in-Chief Dr. Wafik S. El-Deiry from Brown University.The researchers tested PG3 on cancer cell lines with various p53 mutations, as well as on cells that lacked p53 entirely.Full blog - https://www.oncotarget.org/2024/12/18/a-new-path-to-tumor-suppression-the-promise-of-pg3/Paper DOI - https://doi.org/10.18632/oncotarget.28637Correspondence to - Wafik S. El-Deiry - wafik@brown.eduVideo short - https://www.youtube.com/watch?v=eBp_UGrkii8Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28637Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, mutant p53, integrated stress response (ISR), ATF4, HRI, ClpPAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - December 11, 2024 – A #news feature on the #research paper “Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition” by Rackear et al. was #published in Oncotarget's Volume 15 on November 22, 2024, titled “Advancements in cell-penetrating monoclonal antibody treatment."This new publication by Sai Pallavi Pradeep and Raman Bahal from the Department of Pharmaceutical Sciences at the University of Connecticut highlights significant advancements in monoclonal antibody (mAb) therapies. The focus is on the 3E10 antibody, originally derived from autoimmune mouse studies in systemic lupus erythematosus. Unlike traditional mAbs, which struggle to reach intracellular targets, this cell-penetrating antibody targets cancer cells by addressing a major limitation of current therapies. By targeting RAD51, a key intracellular protein involved in DNA repair, the 3E10 antibody shows great promise for cancer treatment, particularly in cancers with defective DNA repair pathways.mAbs have already changed the landscape of cancer therapy, offering treatments that are more targeted and have fewer side effects compared to chemotherapy. However, current therapies are limited since mAbs only target proteins on the surface of cancer cells. This research pushes the boundaries by demonstrating how 3E10 antibodies can penetrate cells and access their internal molecules. This unique capability expands the potential of mAb therapies and targeted cancer treatments.Different humanized versions of the 3E10 antibody were created and carefully tested. Some versions were particularly effective at blocking RAD51, while others showed promise for carrying other therapeutic molecules like genetic material into the cancer cells. This flexibility means that 3E10 could be used to treat different cancer types and deliver various therapeutic molecules directly into tumor cells. This progress offers exciting new possibilities for treating cancer tumors that are resistant to conventional therapies. In conclusion, the 3E10 antibody’s dual function—targeting DNA repair pathways and delivering therapeutic molecules—positions it as a transformative tool in cancer research and targeted cancer treatments.DOI - https://doi.org/10.18632/oncotarget.28674Correspondence to - Raman Bahal - raman.bahal@uconn.eduVideo short - https://www.youtube.com/watch?v=3uMdPvThFHASign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28674Subscribe for free publication alerts from Oncotarget: https://www.oncotarget.com/subscribe/Keywords - cancer, monoclonal anti-bodies, cell penetration, nucleic acid delivery, 3E10About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY - December 9, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on November 22, 2024, entitled “Computed tomography-based radiomics and body composition model for predicting hepatic decompensation." Mayo Clinic researchers Yashbir Singh, John E. Eaton, Sudhakar K. Venkatesh, and Bradley J. Erickson have developed an innovative AI tool to predict hepatic decompensation in individuals with primary sclerosing cholangitis (PSC). PSC is a chronic disease that damages the bile ducts and can lead to liver failure.Hepatic decompensation marks a critical stage of advanced liver disease, and clinicians have long faced challenges in predicting who is at risk. The Mayo Clinic's new AI tool addresses this gap by combining body fat and muscle composition data with insights extracted from computed tomography (CT) scans using computational radiomics. By analyzing these tissues, the AI model identifies patterns linked to an increased risk of liver failure.The study involved 80 PSC patients, including 30 with hepatic decompensation, 30 without, and 20 patients in an external validation set. The AI model achieved impressive results, correctly identifying at-risk patients with 97% accuracy. By recognizing these risks early, clinicians may be able to intervene sooner and improve patient outcomes.While the study focused on PSC, the team emphasized the broader implications of their work.“It may hold promise for the detection of other PSC-related complications, such as cholangiocarcinoma, as well as applications in more prevalent chronic liver diseases like non-alcoholic fatty liver disease (NAFLD).”This non-invasive, data-driven approach offers a powerful way to assess health risks and provide more tailored treatments. Despite the promising findings, the researchers acknowledge the limitations of the study, which include a limited sample size and a single-center design. “However, further research is necessary to validate our findings on a large-scale, independent dataset, ensuring the robustness and generalizability of the model.”In conclusion, this study shows how detailed information from CT scans can help clinicians predict severe liver problems in patients with PSC. By identifying hidden patterns in the images, they can better understand risks and create personalized treatment plans. This approach could improve care for PSC and other long-term liver diseases.DOI - https://doi.org/10.18632/oncotarget.28673Correspondence to - Bradley J. Erickson - bje@mayo.eduVideo short - https://www.youtube.com/watch?v=QCekNtYni4wSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28673Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, radiomics, body composition, machine learning, primary sclerosing cholangitis, computer tomographyAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
“Precision medicine is an innovative approach to disease prevention and treatment that considers differences in people’s genes, injuries, environments, and lifestyles to target the right therapies to the right patients at the right time.”Could a deeper understanding of one of the deadliest lung cancers lead to more effective treatments? Recent research offers a promising way forward, aiming to improve patient outcomes and provide clinicians with valuable insights.Small Cell Lung Cancer (SCLC) is a particularly aggressive form of lung cancer. It spreads fast and does not always respond well to conventional therapies such as chemotherapy. Although SCLC accounts for around 15% of all lung cancer cases, survival rates are extremely low. Only less than 5% of patients live more than five years after diagnosis. These alarming statistics highlight the critical need for new treatments. A team of researchers from the Federal University of Ceará, working together with collaborators from Argentina and Spain, may have found part of the solution.Full blog - https://www.oncotarget.org/2024/12/04/small-cell-lung-cancer-advancing-precision-medicine-with-biomarker-research/Paper DOI - https://doi.org/10.18632/oncotarget.28660Correspondence to - Fabio Tavora - fabio.tavora@argospatologia.comAuthor interview - https://www.youtube.com/watch?v=bJO2MD8AXkYSign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28660Subscribe for free publication alerts from Oncotarget: https://www.oncotarget.com/subscribe/Keywords - cancer, DLL3, pathology, biomarkers, qupath, small cell carcinomaAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - December 4, 2024 – A new #editorial was #published in Oncotarget's Volume 15 on November 22, 2024, entitled “B7-H4: A potential therapeutic target in adenoid cystic carcinoma." Researchers Luana Guimaraes de Sousa and Renata Ferrarotto from The University of Texas MD Anderson Cancer Center made an important discovery about adenoid cystic carcinoma (ACC), a rare and aggressive cancer of the secretory glands. The study found that B7-H4, an inhibitory immune checkpoint, helps ACC tumors avoid attacks from the immune system. This discovery could lead to new treatments for ACC, which currently has very limited options for patients, especially when the cancer spreads to other organs.ACC is known for behaving in two distinct ways. The aggressive form, called ACC-I, spreads quickly to organs like the liver and lungs and leads to a short survival time of approximately three years. The less aggressive form, ACC-II, grows more slowly and often allows patients to live much longer, sometimes over 20 years. However, treatment options for both forms are limited, and once the cancer spreads, it becomes difficult to treat.The study showed that the protein B7-H4 is found at high levels in the aggressive ACC-I tumors. This protein blocks immune cells from entering the tumor, allowing the cancer to grow without being attacked by the immune system. Patients with high levels of B7-H4 in their tumors were found to have worse survival outcomes.To explore possible treatments, the researchers tested a new drug called AZD8205, designed to specifically target and block B7-H4. In preclinical tests on mice, the drug showed remarkable success. Tumors derived from patients shrank in every case, and in many cases of aggressive ACC, the tumors disappeared completely. Importantly, the drug had little effect on less aggressive ACC-II tumors, which have lower levels of B7-H4. This shows that the treatment is highly specific to tumors with high B7-H4 levels. These results have already led to clinical trials that are testing similar drugs in patients with ACC. “These trials represent attractive, rationale therapeutic opportunities for patients facing this rare, aggressive, and chemo-refractory disease, for which no systemic therapy is currently available.”In conclusion, this discovery represents a significant breakthrough in ACC research, identifying B7-H4 as a crucial factor in cancer growth and immune evasion. By leading the way for personalized treatments, it offers promising new therapeutic options and the potential for improved outcomes for ACC patients.DOI - https://doi.org/10.18632/oncotarget.28661Correspondence to - Renata Ferrarotto - rferrarotto@mdanderson.orgSign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28661Subscribe for free publication alerts from Oncotarget: https://www.oncotarget.com/subscribe/About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - December 3, 2024 – A new #review was #published in Oncotarget's Volume 15 on November 22, 2024, entitled “Mesenchymal stem cells - the secret agents of cancer immunotherapy: Promises, challenges, and surprising twists." Authored by Theia Minev, Shani Balbuena, Jaya Mini Gill, Francesco M. Marincola, Santosh Kesari, and Feng Lin from CureScience Institute, Sonata Therapeutics, and Pacific Neuroscience Institute and Providence Saint John’s Health Center, this review explores the potential role of mesenchymal stem cells (MSCs) in cancer treatment. These stem cells can naturally target tumors and deliver therapeutic agents directly to cancer cells, potentially improving treatment outcomes while reducing side effects commonly associated with traditional therapies like chemotherapy. However, the authors also note significant challenges, pointing out that under certain conditions, MSCs may unintentionally promote tumor growth, highlighting the need for careful therapeutic design.MSCs are cells that can develop in different types of tissues, such as bone, fat, or cartilage, and act as natural repair agents. What makes them particularly special is their ability to respond to biological signals, like inflammation, which is often present in cancer. This enables them to locate tumors, and once there, they can deliver cancer treatments directly to the affected area.Clinical trials are already investigating MSC-based treatments for cancers such as brain tumors, melanoma, and ovarian cancer. Some results are promising, showing that MSCs can effectively deliver treatments and boost the immune system’s fight against cancer. However, other trials have also revealed the complexities of MSC behavior, including variability in their effects and the potential to create conditions that support tumor growth. “This variability may be due to the tumor immune microenvironment’s effects, where immune cells are inhibited by various factors, creating a conducive environment for tumor growth.” The authors also suggest that “Developing personalized MSC therapies tailored to the specific characteristics of a patient’s tumor and immune system could enhance the efficacy and safety of MSC-based treatments.” Achieving this requires a deeper understanding of how MSCs interact with cancer cells and their surrounding environment.In conclusion, this review highlights both the potential and challenges of (MSCs in cancer therapy. With ongoing research and technological advancements, MSCs could become a key component of personalized cancer treatments, offering new hope for patients worldwide.DOI - https://doi.org/10.18632/oncotarget.28672Correspondence to - Feng Lin - flin@curescience.orgVideo short - https://www.youtube.com/watch?v=Wwc3zDDitlcSubscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - November 27, 2024 – A new #editorial was #published in Oncotarget's Volume 15 on November 12, 2024, entitled “Persistence landscapes: Charting a path to unbiased radiological interpretation.”In this editorial, Yashbir Singh, Colleen Farrelly, Quincy A. Hathaway, and Gunnar Carlsson from the Department of Radiology, Mayo Clinic (Rochester, MN), introduce persistence landscapes, a mathematical method designed to address biases in medical imaging and artificial intelligence (AI). Persistence landscapes build on persistence images, which track how patterns in data appear and disappear across different scales. By transforming this complex data into simpler, more manageable forms, persistence landscapes create a format that is easy to analyze and compare. This makes it a valuable tool for identifying and correcting biases in medical imaging.Medical imaging plays a critical role in healthcare, but it is not perfect. Biases, caused by differences in equipment, technology, or even the patient population, can lead to inaccurate diagnoses. Persistence landscapes offer a way to identify and fix these hidden issues. "[...] persistence landscapes have the potential to play a crucial role in identifying and mitigating biases in radiological practice, whether these biases stem from demographic factors, equipment variations, or the limitations of AI algorithms.”Persistence landscapes are particularly effective at reducing random noise in medical images while preserving important details. This makes it easier for clinicians and researchers to focus on the most meaningful parts of an image. The method also improves AI tools by addressing common problems, such as when models are too focused on specific details or when they miss important information. Additionally, persistence landscapes also simplify the integration of data from different scan types, like positron emission tomography (PET) and magnetic resonance imaging (MRI), without introducing new errors.Despite its potential, the use of persistence landscapes in real-world medical imaging comes with challenges. It requires powerful computers to process large data, which can be costly and time-consuming, and expert interpretation for meaningful use. Better tools are needed to make this method more accessible for clinicians. While integrating this method into clinical settings will take effort, the benefits could be transformative. With further research and refinement, persistence landscapes hold enormous promise for advancing equitable healthcare.“Persistence landscapes represent a powerful new tool in our ongoing efforts to achieve unbiased and accurate radiological interpretation.”DOI - https://doi.org/10.18632/oncotarget.28671Correspondence to - Yashbir Singh - singh.yashbir@mayo.eduVideo short - https://www.youtube.com/watch?v=kq1pEhZvLXcSubscribe for free publication alerts from Oncotarget: https://www.oncotarget.com/subscribe/About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - November 25, 2024 – A new #editorial was #published in Oncotarget's Volume 15 on November 12, 2024, entitled, “Visualizing radiological data bias through persistence images.”This editorial highlights a powerful tool called "persistence images," which could improve how medical imaging and artificial intelligence (AI) systems are developed and used. Authors Yashbir Singh, Colleen Farrelly, Quincy A. Hathaway, and Gunnar Carlsson from the Department of Radiology, Mayo Clinic (Rochester, MN), provide a detailed explanation of how persistence images uncover hidden biases and advance fairness in healthcare AI.AI is becoming a major part of healthcare, helping clinicians analyze X-rays, magnetic resonance imaging, and computed tomography scans. However, if the data used to train AI systems is biased, it could lead to unfair or inaccurate results. Derived from topological data analysis (TDA), persistence images transform complex medical scans into simple, stable visuals. These images make it easier to spot patterns or irregularities that could indicate bias. For example, they can reveal whether certain groups—such as patients of a specific age, gender, or ethnicity—are underrepresented in the data used to train AI systems.“The use of persistence images in radiological analysis opens up new possibilities for identifying and addressing biases in both data interpretation and AI model training...” This could help ensure that AI systems work equitably for all patient groups, resulting in more reliable diagnoses and better outcomes.In addition to detecting bias, persistence images also help filter out noise, or irrelevant details, from medical scans. This makes it easier for both AI systems and radiologists to focus on meaningful features in the images, improving overall accuracy. These insights help AI systems perform better and make more accurate, trustworthy decisions.Despite their potential, persistence images face challenges. Generating persistence images for large datasets demands substantial computing power, while integration into clinical workflows requires user-friendly tools and specialized training for healthcare professionals.As healthcare becomes more data-driven, tools like persistence images could transform how medical imaging is used. “By helping us visualize and address hidden biases, they can contribute to improved patient outcomes and more personalized healthcare delivery.”In conclusion, this editorial envisions a future where advanced mathematical tools like persistence images play a vital role in eliminating bias and improving patient outcomes. Integrating these tools into clinical workflows could enhance radiological analysis, setting new standards for accuracy and equity in healthcare worldwide.DOI - https://doi.org/10.18632/oncotarget.28670Correspondence to - Yashbir Singh - singh.yashbir@mayo.eduVideo short - https://www.youtube.com/watch?v=sQELv8oi3ewAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - November 20, 2024 – A new #editorial was #published in Oncotarget's Volume 15 on November 12, 2024, entitled, “Persistence barcodes: A novel approach to reducing bias in radiological analysis.”This editorial, authored by Yashbir Singh, Colleen Farrelly, Quincy A. Hathaway and Gunnar Carlsson from the Department of Radiology, Mayo Clinic (Rochester, MN), introduces persistence barcodes as a groundbreaking tool in medical imaging, particularly radiology.Derived from topological data analysis (TDA), this method transforms complex medical images into clear, interpretable patterns. By highlighting features such as tissue densities, blood vessels, and tumors, persistence barcodes reduce diagnostic bias and uncover subtle details that traditional artificial intelligence (AI) systems might miss. This innovative approach holds great promise for enhancing diagnostic accuracy and improving patient care.Unlike some AI tools, like Graph Neural Networks, which risk oversmoothing and blurring critical features, persistence barcodes preserve key structural details. This method visualizes how features in medical images emerge, persist, and fade across different scales, providing clearer insights into the data.By detecting subtle changes in tissue density that could indicate early disease and filtering out irrelevant artifacts or noise from imaging errors, persistence barcodes enhance diagnostic accuracy and reliability.Persistence barcodes enhance fairness and consistency by standardizing analyses across different machines and radiologists, ensuring reliable diagnoses regardless of the imaging system. Their robustness against equipment-related variations makes them a valuable tool for improving diagnostic accuracy in diverse clinical settings.While promising, the integration of persistence barcodes into routine medical practice faces challenges, such as the computational demands of processing high-resolution images and the need for user-friendly visualization tools. “As we continue to refine and validate this approach, persistence barcodes could play a crucial role in developing more accurate, consistent, and unbiased diagnostic tools. This, in turn, has the potential to improve patient outcomes and advance the field of radiology as a whole.” In conclusion, with continued development and refinement, persistence barcodes have the potential to revolutionize medical imaging by facilitating earlier and more accurate disease detection, minimizing diagnostic errors, and significantly improving patient outcomes.DOI - https://doi.org/10.18632/oncotarget.28667Correspondence to - Yashbir Singh - singh.yashbir@mayo.eduVideo short - https://www.youtube.com/watch?v=eVOqpV2vFsgSubscribe for free publication alerts from Oncotarget: https://www.oncotarget.com/subscribe/About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
Samuel Silva from the Department of Pathology at Federal University of Ceará in Fortaleza, Brazil, discusses a research paper he co-authored that was published in Oncotarget Volume 15, titled, “Relationship between the expressions of DLL3, ASC1, TTF-1 and Ki-67: First steps of precision medicine at SCLC.”DOI - https://doi.org/10.18632/oncotarget.28660Correspondence to - Fabio Tavora - fabio.tavora@argospatologia.comVideo interview - https://www.youtube.com/watch?v=bJO2MD8AXkYVideo transcription - https://www.oncotarget.net/2024/11/18/behind-the-study-dll3-asc1-ttf-1-ki-67-in-precision-medicine-for-sclc/Sign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28660Subscribe for free publication alerts from Oncotarget: https://www.oncotarget.com/subscribe/Keywords - cancer, DLL3, pathology, biomarkers, qupath, small cell carcinomaAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - November 18, 2024 – A new #editorial was #published in Oncotarget's Volume 15 on November 12, 2024, entitled, “Mitigating bias in radiology: The promise of topological data analysis and simplicial complexes.”In this publication, researchers Yashbir Singh, Colleen Farrelly, Quincy A. Hathaway, and Gunnar Carlsson from the Department of Radiology at the Mayo Clinic in Rochester, MN, explore how a mathematical technique called Topological Data Analysis (TDA) can enhance the reliability and reduce bias in AI systems used for medical diagnosis. By addressing issues of fairness and accuracy in current AI tools, TDA holds the potential to transform the field of radiology.Radiology increasingly relies on AI to analyze medical images like X-rays and Magnetic Resonance Imaging (MRIs). While these tools provide speed and efficiency, they can sometimes yield biased or inconsistent results due to limitations in the data or algorithms. Researchers suggest that TDA can address these challenges by capturing critical details in medical images—such as subtle tissue patterns or branching structures in blood vessels—that traditional methods might overlook.TDA analyzes the "shape" and structure of data, which uncovers patterns and relationships beyond individual pixels. This innovative approach offers three key benefits: 1) It captures intricate features, such as looping blood vessels, 2) provides a more comprehensive analysis by examining interactions between pixel groups, creating a holistic view, and 3) enhances transparency that allows clinicians to better understand how AI reaches its conclusions and identify potential errors or biases.AI tools in radiology are often trained on limited or unbalanced data, meaning they might not work as well for certain groups of people. This can lead to unfair or inaccurate diagnoses. TDA offers a way to fix that by creating more comprehensive and diverse data models. It can also handle noise and inconsistencies in images, like differences caused by different equipment or patient positions. “This mathematical framework has the potential to significantly improve the accuracy and fairness of radiological assessments, paving the way for more equitable patient care.”In conclusion, this new approach has the potential to revolutionize how AI is used in radiology and improve diagnosis for everyone. While still in early development, researchers are optimistic about TDA’s ability to transform medical imaging. “As researchers and clinicians, we must continue to explore and develop these innovative approaches to ensure that the future of AI-assisted radiology is both highly accurate and equitable for all patients.”DOI - https://doi.org/10.18632/oncotarget.28668Correspondence to - Yashbir Singh - singh.yashbir@mayo.eduVideo short - https://www.youtube.com/watch?v=v7eWFjmKoNkSubscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
Cancer dormancy is a phenomenon in which, after treatment, residual cancer cells remain inactive in the body for months or even years. During this time, patients often show no signs of the disease. These dormant cells can unpredictably reawaken, leading to tumor recurrence—a significant challenge in cancer treatment. Despite progress in cancer research, the factors that control dormancy and subsequent reactivation remain poorly understood. Identifying these factors and understanding how cancer cells dormancy and reactivation occur could be crucial to preventing cancer recurrence. This question was the focus of a recent study titled “Initiation of Tumor Dormancy by the Lymphovascular Embolus,” published in Oncotarget Volume 15, on October 11, 2024. In this blog, we will look at the key findings and implications of this important work.Full blog - https://www.oncotarget.org/2024/11/13/cancer-dormancy-and-tumor-recurrence-new-insights-for-breast-cancer/Research paper DOI - https://doi.org/10.18632/oncotarget.28658Correspondence to - Sanford H. Barsky - sbarsky@mmc.eduVideo short - https://www.youtube.com/watch?v=z6ex7Yl8r5QSign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28658Subscribe for free publication alerts from Oncotarget: https://www.oncotarget.com/subscribe/Keywords - cancer, dormancy, lymphovascular embolus, mTOR, E-cadherin proteolysisAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - November 12, 2024 – A new #review was #published in Oncotarget's Volume 15 on November 7, 2024, entitled “Understanding the interplay between extracellular matrix topology and tumor-immune interactions: Challenges and opportunities.”This comprehensive review by researchers Yijia Fan, Alvis Chiu, Feng Zhao, and Jason T. George from Texas A&M University, Rice University, and MD Anderson Cancer Center sheds light on how the structural properties of the extracellular matrix (ECM) within tumors impact immune cell behavior and influence the effectiveness of cancer immunotherapies. The ECM, a network of proteins surrounding cells, often transforms in cancer, becoming denser and more aligned. These changes create physical barriers that can prevent immune cells, especially T cells, from effectively accessing and attacking tumors, thereby limiting the success of immunotherapies.The team emphasizes the role of specific ECM configurations, known as Tumor-Associated Collagen Signatures (TACS), in cancer progression and immune evasion. TACS1 and TACS2 patterns create "immune deserts" around tumors, limiting immune cell movement and preventing T cells from recognizing and attacking cancer cells, which is essential for successful immunotherapy. In advanced stages, TACS3 aligns ECM fibers in ways that both promote tumor spread and create additional barriers, further obstructing immune cell access to the tumor.These insights lead the way for ECM-targeted therapies designed to modify these barriers, potentially transforming “cold” (immune-non-responsive) tumors into “hot” (immune-responsive) ones, thereby improving immune cell infiltration and enhancing treatment outcomes. “Understanding the complex interplay is relevant for developing more accurate model of tumor evasion and the identification of corresponding therapeutic intervention.”The review highlights advanced computational models that simulate interactions between the ECM, immune cells, and tumors, offering valuable insights for developing ECM-targeted therapies. These models illustrate how modifying ECM properties could enhance immune cell migration and function, potentially overcoming immune resistance and expanding the effectiveness of immunotherapies.The authors also suggest that targeting ECM structure could significantly enhance the effectiveness of immunotherapy, especially for cancers like breast, pancreatic, and ovarian, which often feature dense ECM regions. By reshaping the ECM, such treatments could enable immune cells to access previously unreachable tumor areas, presenting a promising strategy to combat tumors that are resistant to standard therapies.In conclusion, the review underscores the need for continued research into ECM-focused strategies, which could support more integrated approaches to cancer treatment. By targeting the ECM’s physical barriers and immune evasion mechanisms, these strategies hold promise for improving outcomes in difficult-to-treat cancers.DOI - https://doi.org/10.18632/oncotarget.28666Correspondence to - Jason T. George - jason.george@tamu.eduVideo short - https://www.youtube.com/watch?v=7Wm-SMLJadkSign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28666Subscribe for free publication alerts from Oncotarget: https://www.oncotarget.com/subscribe/To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - November 11, 2024 – A new #editorial was #published in Oncotarget's Volume 15 on November 7, 2024, titled “Beyond the hype: Navigating bias in AI-driven cancer detection.”In this editorial, researchers from the Mayo Clinic emphasize the need to address potential biases in Artificial Intelligence (AI) tools used for cancer detection to ensure fair and equitable healthcare. Authors Yashbir Singh, Heenaben Patel, Diana V. Vera-Garcia, Quincy A. Hathaway, Deepa Sarkar, and Emilio Quaia discuss the risks of biased AI systems, which can lead to disparities in diagnosis and treatment outcomes across diverse patient groups.While AI is transforming cancer care through early diagnosis and improved treatment planning, this study warns that AI models trained on limited or non-diverse data may misdiagnose or overlook certain populations, particularly those in underserved communities, thereby increasing healthcare disparities. As explained in the editorial, “For example, if an AI model is trained on Caucasian patients, it may struggle to detect skin cancer accurately in patients with darker skin, leading to missed diagnoses or false positives.” Such biases could result in unequal access to early diagnosis and treatment, ultimately leading to poorer health outcomes for certain groups. Beyond racial bias, factors such as socioeconomic status, gender, age, and geographic location can also affect the accuracy of AI in healthcare.The authors propose a comprehensive approach to developing fair AI models in healthcare, highlighting six key strategies. They first emphasize the importance of using diverse and representative datasets to improve diagnostic accuracy across all demographics. Rigorous testing and validation across various population groups are necessary before AI systems are widely implemented. To promote ethical AI use, models should be transparent in their decision-making processes, enabling clinicians to recognize and address potential biases. The researchers also advocate for collaborative development involving data scientists, clinicians, ethicists, and patient advocates to capture a range of perspectives. Continuous monitoring and regular audits are essential to detect and correct biases over time. Finally, training healthcare providers on AI’s strengths and limitations will empower them to use these tools responsibly and make informed interpretations.“The goal should not merely be to create AI systems that are more accurate than humans but to develop technologies that are fundamentally fair and beneficial to all patients.”The authors also urge regulatory bodies, such as the U.S. Food and Drug Administration (FDA), to implement updated frameworks specifically aimed at addressing AI bias in healthcare. Policies that promote diversity in clinical trials and incentivize the development of fair AI systems will help ensure that AI benefits reach all populations equitably. They caution against over-reliance on AI without a full understanding of its limitations, as unchecked biases could undermine patient trust and slow the adoption of valuable AI technologies.In conclusion, as AI continues to transform cancer care, the healthcare sector must prioritize fairness, transparency, and robust AI regulation to ensure that it serves all patients without bias. By addressing bias from development through to implementation, AI can fulfill its promise of creating a fair and effective healthcare system for everyone.DOI - https://doi.org/10.18632/oncotarget.28665Correspondence to - Yashbir Singh - singh.yashbir@mayo.eduTo learn more about Oncotarget, please visit https://www.oncotarget.com.MEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - November 6, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on October 11, 2024, entitled “Relationship between the expressions of DLL3, ASC1, TTF-1 and Ki-67: First steps of precision medicine at SCLC”This study, led by researchers from the Federal University of Ceará in Brazil and collaborating institutions in Brazil, Argentina and Spain, presents important findings on small cell lung cancer (SCLC), one of the most aggressive forms of lung cancer with limited treatment options. The research reveals how specific biomarkers in SCLC tumors could open new opportunities for more personalized and targeted therapies for these patients.SCLC accounts for about 15% of all lung cancer cases and is known for its rapid spread and resistance to many treatments. Currently, the five-year survival rate for SCLC patients is below 5%. Recent advances in precision medicine aim to improve these outcomes by identifying and targeting the unique characteristics of each patient’s tumor.Researchers Samuel Silva, Juliana C. Sousa, Cleto Nogueira, Raquel Feijo, Francisco Martins Neto, Laura Cardoso Marinho, Guilherme Sousa, Valeria Denninghoff, and Fabio Tavora analyzed tumor samples from 64 SCLC patients using both traditional and digital pathology tools. Their findings highlighted promising results for two of the analyzed biomarkers: Delta-like ligand 3 (DLL3) and Thyroid transcription factor-1 (TTF-1).DLL3 was identified in over 70% of the tumors, highlighting its potential as a promising target for therapies like Tarlatamab. Another key finding involved TTF-1 expression; patients with TTF-1-positive tumors showed improved survival rates, underscoring its potential as a prognostic marker to refine diagnoses and predict patient outcomes.The authors also noted that, “The use of digital pathology software QuPath enhanced the accuracy and depth of analysis, allowing for detailed morphometric analysis and potentially informing more personalized treatment approaches.”In conclusion, the study suggests that clinical trials targeting biomarkers like DLL3 and TTF-1 could enhance SCLC patient outcomes by tailoring treatments based on individual biomarker profiles. This research marks an important step forward in precision medicine for SCLC.DOI - https://doi.org/10.18632/oncotarget.28660Correspondence to - Fabio Tavora - fabio.tavora@argospatologia.comVideo short - https://www.youtube.com/watch?v=YYsZ0UHPszgSign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28660Subscribe for free publication alerts from Oncotarget: https://www.oncotarget.com/subscribe/Keywords - cancer, DLL3, pathology, biomarkers, qupath, small cell carcinomaAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - November 4, 2024 – A new #casereport was #published in Oncotarget's Volume 15 on October 11, 2024, entitled “A case of adenosquamous pancreatic cancer with a KRAS G12C mutation with an exceptional response to immunotherapy.”This case report highlights a remarkable and unexpected response to immunotherapy in a patient with metastatic adenosquamous pancreatic cancer (ASCP), a rare and aggressive form of pancreatic cancer. The study, led by Murtaza Ahmed, Brent K. Larson, Arsen Osipov, Nilofer Azad, and Andrew Hendifar from Cedars-Sinai Medical Center and Johns Hopkins University, provides new hope for ASCP patients, who are traditionally underserved by current treatment options.The team documented a 68-year-old male with metastatic ASCP carrying a KRAS G12C mutation. Unexpectedly, after limited success with standard therapies, the patient’s cancer responded significantly to pembrolizumab, a type of immune checkpoint inhibitor, despite the absence of typical markers indicating suitability for immunotherapy.Pancreatic cancer remains one of the most lethal cancer types, with few advancements in effective treatments for its rarer forms, such as ASCP, which accounts for only 1-10% of all pancreatic cancer cases. Traditionally, ASCP has been treated with chemotherapy based on protocols for the more common pancreatic ductal adenocarcinoma, despite the distinct tumor characteristics. This case suggests that ASCP’s unique tumor microenvironment may make it more receptive to immunotherapy. Researchers are hopeful that this new understanding will drive clinical trials focused on immunotherapy specifically for ASCP patients, potentially offering new options for those with limited treatment success. “To that point, there is an active multi-center phase 2 trial investigating outcomes and responses to ICI in patients with metastatic or unresectable ASCP or ampullary cancer.” In conclusion, this report signals a potential shift in the treatment of rare and aggressive pancreatic cancer subtypes like ASCP. As oncology increasingly embraces personalized medicine, cases like this one open new avenues for patients who were not responsive to traditional therapies, potentially transforming the management of previously intractable cancers.DOI - https://doi.org/10.18632/oncotarget.28659Correspondence to - Andrew Hendifar - andrew.hendifar@cshs.orgVideo short - https://www.youtube.com/watch?v=VnfohGvfMoMSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28659Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, pancreatic cancer, immunotherapy, metastasisAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- October 30, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on October 11, 2024, entitled “Initiation of tumor dormancy by the lymphovascular embolus.”Researchers Yin Ye, Justin Wang, Michael G. Izban, Billy R. Ballard, and Sanford H. Barsky from Meharry Medical College in Nashville, TN, and Scripps Mercy Hospital in San Diego, CA, uncovered critical mechanisms that lead to tumor dormancy in breast cancer. This study sheds light on how certain cancer cells can remain dormant for years before potentially reawakening as metastatic tumors.Using breast cancer patient-derived organoids and tumor samples, the research team discovered that tumor dormancy in breast cancer can be triggered by specific signaling changes within small cell clusters, called tumor emboli, which detach from the primary tumor and travel through the bloodstream. These emboli can remain inactive, sometimes for years, before reawakening in other parts of the body. Key changes include reduced activity of mTOR, a metabolic regulator, and structural shifts in E-cadherin, a molecule involved in cell adhesion. This study also suggests these changes are regulated by the PI3K pathway and occur within the unique three-dimensional structure of tumor spheroids, shedding light on the interactions within dormant cell clusters.As a conclusion, this work not only identifies mTOR and E-cadherin as key components in maintaining dormancy but also offers a promising roadmap for future therapies. By targeting these pathways, there may be potential to keep cancer cells in a dormant state, reducing the risk of late-stage recurrence and improving patient outcomes.DOI - https://doi.org/10.18632/oncotarget.28658Correspondence to - Sanford H. Barsky - sbarsky@mmc.eduVideo short - https://www.youtube.com/watch?v=z6ex7Yl8r5QSign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28658Subscribe for free publication alerts from Oncotarget: https://www.oncotarget.com/subscribe/Keywords - cancer, dormancy, lymphovascular embolus, mTOR, E-cadherin proteolysisAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- October 29, 2024 – A new #casereport was #published in Oncotarget's Volume 15 on October 11, 2024, entitled “Complete response to encorafenib plus binimetinib in a BRAF V600E-mutant metastasic malignant glomus tumor.”As highlighted in the abstract, glomus tumors (GT) are rare mesenchymal neoplasms originating in dermal arteriovenous structures involved in thermoregulation. While generally benign, some can exhibit malignant features, leading to aggressive behavior, metastasis, and limited response to standard chemotherapy. The identification of the BRAF V600E mutation in certain malignant GT cases offers a promising therapeutic target.In their paper, researchers Marta Arregui, Antonio Calles, María del Mar Galera, Ana Gutiérrez, Carlos López-Jiménez, Carolina Agra, Adriana Fernández, Natalia Gutiérrez, María de Toro and Rosa Álvarez from Gregorio Marañón University Hospital and Fundación Jiménez Díaz University Hospital in Madrid, Spain, document a remarkable clinical and metabolic response in a case of metastatic BRAF V600E-mutated glomangiosarcoma treated with the combination of encorafenib and binimetinib. They report on a 45-year-old male patient with stage IV malignant GT carrying a BRAF V600E mutation, who was treated systemically with encorafenib and binimetinib. This approach led to a swift clinical and radiological improvement.“To our knowledge, our patient represents the first reported case of a metastatic malignant GT successfully treated with BRAF and MEK inhibitors, achieving a long-lasting complete morpho-metabolic response.”DOI - https://doi.org/10.18632/oncotarget.28654Correspondence to - Carlos López-Jiménez - clopezjimenez@atbsarc.orgVideo short - https://www.youtube.com/watch?v=xjbj3Iu16P4Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28654Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, malignant glomus tumor, glomangiosarcoma, BRAF V600E, agnostic treatment, targeted therapyAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
Drs. Mehdi Mollapour, Jennifer Heritz, and Sarah Backe from SUNY Upstate Medical University (Syracuse, NY) discuss a review they co-authored that was published by Oncotarget in Volume 15, entitled, “Molecular chaperones: Guardians of tumor suppressor stability and function.”DOI - https://doi.org/10.18632/oncotarget.28653Correspondence to - Mehdi Mollapour - mollapom@upstate.eduVideo interview - https://www.youtube.com/watch?v=vEHmyemWgNoVideo transcript - https://www.oncotarget.net/2024/10/24/behind-the-study-molecular-chaperones-tumor-suppressor-stability/AbstractThe term ‘tumor suppressor’ describes a widely diverse set of genes that are generally involved in the suppression of metastasis, but lead to tumorigenesis upon loss-of-function mutations. Despite the protein products of tumor suppressors exhibiting drastically different structures and functions, many share a common regulatory mechanism—they are molecular chaperone ‘clients’. Clients of molecular chaperones depend on an intracellular network of chaperones and co-chaperones to maintain stability. Mutations of tumor suppressors that disrupt proper chaperoning prevent the cell from maintaining sufficient protein levels for physiological function. This review discusses the role of the molecular chaperones Hsp70 and Hsp90 in maintaining the stability and functional integrity of tumor suppressors. The contribution of cochaperones prefoldin, HOP, Aha1, p23, FNIP1/2 and Tsc1 as well as the chaperonin TRiC to tumor suppressor stability is also discussed. Genes implicated in renal cell carcinoma development—VHL, TSC1/2, and FLCN—will be used as examples to explore this concept, as well as how pathogenic mutations of tumor suppressors cause disease by disrupting protein chaperoning, maturation, and function.Sign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28653Subscribe for free publication alerts from Oncotarget: https://www.oncotarget.com/subscribe/Keywords - cancer, molecular chaperone, tumor suppressor, renal cell carcinoma, Birt-Hogg-Dubé (BHD) syndrome, TSC syndromeAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
Cancer research has made remarkable progress in recent years, with monoclonal antibody (mAb) therapy emerging as one of the most promising advancements. These treatments are designed to precisely target cancer cells, offering a more focused approach that helps patients fight different malignancies with fewer side effects compared to traditional chemotherapy.Despite this progress, a major challenge remains: targeting cancer-related molecules inside cells rather than on the surface, which has been the main focus of available mAb therapies until now. This is where the groundbreaking research in the paper “Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition,” published in Volume 15 of Oncotarget on October 1, 2024, comes into play.Full blog - https://www.oncotarget.org/2024/10/24/next-generation-antibodies-for-cancer-therapy/Paper DOI - https://doi.org/10.18632/oncotarget.28651Correspondence to - Peter M. Glazer - peter.glazer@yale.eduVideo short - https://www.youtube.com/watch?v=sTHjJ0Qq0YQSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28651Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, 3E10, cell penetration, nucleic acid binding, nucleic acid delivery, RAD51About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- October 23, 2024 – A new #editorial was #published in Oncotarget's Volume 15 on October 11, 2024, entitled, “Gene regulatory network and signalling pathway rewiring: How blood cancer cells shift their shapes to evade drug treatment.”As highlighted in the paper, Acute Myeloid Leukemia (AML) is a complex and diverse disease caused by multiple mutations in genes that regulate transcription and growth. These mutations lead to extensive rewiring of the gene regulatory network (GRN), which alters the identity of hematopoietic stem and progenitor cells, ultimately blocking normal myeloid differentiation. A key feature of AML is the presence of mutations in growth factor receptor and signaling genes, such as FLT3, KIT, and RAS. Notably, FLT3 is one of the most commonly mutated genes in AML, with around 25% of cases showing an internal tandem duplication (ITD) that causes the receptor to remain constantly active.In their paper, researchers Constanze Bonifer and Peter N. Cockerill from the Institute of Cancer and Genomic Sciences at the University of Birmingham, UK, and the Murdoch Children’s Research Institute, Royal Children’s Hospital in Melbourne, Australia, discuss recent publications from their group addressing this issue through a multi-omics study. The authors investigated how gene regulatory networks (GRNs) in FLT3-ITD patients were rewired compared to normal cells and in response to FLT3 inhibitor treatment. Several key findings stood out, including: 1) Mapping of open chromatin regions revealed that patients initially responsive to FLT3 inhibition showed significant rewiring of their GRNs, forming new connections between transcription factors (TFs) and target genes, while non-responsive patients did not; 2) Chromatin immunoprecipitation (ChIP) experiments showed that drug treatment led to the loss of binding of RUNX1, the master regulator of hematopoiesis, and the MAP-Kinase (MAPK)-inducible TF AP-1; 3) Disruption of AP-1 binding via a dominant-negative version of the TF (dnFOS) also abolished RUNX1 binding at hundreds of sites, indicating that RUNX1 binding is AP-1 dependent; and 4) Inhibition of both AP-1 and RUNX1 led to a pronounced cell cycle block.“In summary, drugs that target individual signalling pathways in AML often fail to stop proliferation malignant growth, due to the wide variety, redundancy and cross talk between multiple pathways regulating and differentiation.”DOI - https://doi.org/10.18632/oncotarget.28662Correspondence to - Constanze Bonifer - constanze.bonifer@mcri.edu.auVideo short - https://www.youtube.com/watch?v=5c_uT6aE36ASign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28662Subscribe for free publication alerts from Oncotarget: https://www.oncotarget.com/subscribe/Keywords - cancer, acute myeloid leukemia, gene regulatory networks, aberrant growth factor signaling, transcription, RUNX1/AP-1 axisAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh
It is with great sadness and heavy heart that we announce the recent passing of Dr. Mikhail (Misha) V. Blagosklonny, our beloved Editor-in-Chief. Misha succumbed to metastatic lung cancer after a courageous battle.Dr. Blagosklonny will be remembered as a brilliant and extraordinary scientist who dedicated his life to science. He was a visionary thinker, who made highly original contributions to cancer and aging research that were often ahead of their time. Dr. Blagosklonny was born into a family of scientists. His mother, Professor of Medicine Yanina V. Blagosklonnaya, specialized in endocrinology and was a talented teacher, mentoring several generations of medical students. His father, Professor Vladimir M. Dilman, was a brilliant gerontologist, endocrinologist and oncologist, known for being a very charismatic person. He was the first person to encourage Misha to think about nature, aging, and philosophy. Misha was a theorist by nature. While in school, he was deeply interested in physics and dreamed of becoming a theoretical physicist. Eventually, he chose biology, driven to study aging and age-related diseases, including cancer. He started as an experimentalist, but over the years, he became a theoretical biologist. In a way, his dream came true. Full tribute to Misha: https://www.oncotarget.com/news/pr/tribute-to-dr-mikhail-misha-blagosklonny/
BUFFALO, NY- October 21, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on October 1, 2024, entitled, “Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition.”As highlighted in the abstract, monoclonal antibody therapies for cancer have shown extraordinary clinical success in recent years. However, these strategies are primarily limited to targeting specific cell surface antigens, despite many disease targets being located intracellularly.In their paper, researchers Madison Rackear, Elias Quijano, Zaira Ianniello, Daniel A. Colón-Ríos, Adam Krysztofiak, Rashed Abdullah, Yanfeng Liu, Faye A. Rogers, Dale L. Ludwig, Rohini Dwivedi, Franziska Bleichert, and Peter M. Glazer from the Departments of Therapeutic Radiology and Genetics at Yale University School of Medicine, Gennao Bio, and the Department of Molecular Biophysics and Biochemistry at Yale University report on the humanization of the full-length, nucleic acid-binding monoclonal lupus-derived autoantibody 3E10, which exhibits a novel mechanism for cell penetration and tumor-specific targeting.The authors compare humanized variants of 3E10 and demonstrate that cell uptake relies on the nucleoside transporter ENT2. They also find that faster cell uptake and superior in vivo tumor targeting are associated with higher affinity nucleic acid binding.“We show that one human variant retains the ability of the parental 3E10 to bind RAD51, serving as a synthetically lethal inhibitor of homology-directed repair in vitro.”DOI - https://doi.org/10.18632/oncotarget.28651Correspondence to - Peter M. Glazer - peter.glazer@yale.eduVideo short - https://www.youtube.com/watch?v=sTHjJ0Qq0YQSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28651Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, 3E10, cell penetration, nucleic acid binding, nucleic acid delivery, RAD51About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- October 16, 2024 – A new #review was #published in Oncotarget's Volume 15 on October 1, 2024, entitled, “Molecular chaperones: Guardians of tumor suppressor stability and function.”As highlighted in the abstract of this paper, "tumor suppressor" describes a diverse set of genes typically involved in suppressing metastasis, but which can lead to tumorigenesis when loss-of-function mutations occur. Despite the varied structures and functions of tumor suppressor proteins, many share a common regulatory mechanism—they are "clients" of molecular chaperones, and they rely on an intracellular network of chaperones and co-chaperones to maintain their stability. Mutations in tumor suppressors that disrupt proper chaperoning prevent cells from maintaining sufficient protein levels for normal physiological function.In their review, researchers Jennifer A. Heritz, Sarah J. Backe, and Mehdi Mollapour from SUNY Upstate Medical University and New York VA Health Care in Syracuse, New York, discuss the role of molecular chaperones Hsp70 and Hsp90 in maintaining the stability and functional integrity of tumor suppressors. They also detail the contributions of co-chaperones prefoldin, HOP, Aha1, p23, FNIP1/2, and Tsc1, as well as the chaperonin TRiC, to tumor suppressor stability.“Overall, it is clear that oncogenesis can result from the dysregulation of tumor suppressor stabilization by chaperones.”DOI - https://doi.org/10.18632/oncotarget.28653Correspondence to - Mehdi Mollapour - mollapom@upstate.eduVideo short - https://www.youtube.com/watch?v=V5OFjeqaH3ASign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28653Subscribe for free publication alerts from Oncotarget: https://www.oncotarget.com/subscribe/Keywords - cancer, molecular chaperone, tumor suppressor, renal cell carcinoma, Birt-Hogg-Dubé (BHD) syndrome, TSC syndromeAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- October 11, 2024 – A new #editorial was #published in Oncotarget's Volume 15 on October 1, 2024, entitled, “Transplant or no transplant for TP53 mutated AML.”As highlighted in this editorial, TP53 mutations (mut) occur in 10–15% of acute myeloid leukemia (AML) cases, commonly associated with therapy-related AML (t-AML) and complex cytogenetics (CG). TP53-mut AML is inherently resistant to conventional chemotherapies and continues to show a poor prognosis, even with venetoclax-based therapies. Allogeneic hematopoietic stem cell transplant (allo-HCT) remains a potential curative option, though only 10–15% of patients receive it. In a recent study, allo-HCT was the only variable significantly improving survival, despite only 16% of patients successfully bridging to it.In their editorial, researchers Talha Badar, Moazzam Shahzad, Ehab Atallah, Mark R. Litzow, and Mohamed A. Kharfan-Dabaja from the Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program at Mayo Clinic (Jacksonville, Florida) evaluated the outcomes of TP53-mutated AML patients based on data from the Consortium of Myeloid Malignancies and Neoplastic Diseases (COMMAND). The study found a “dismal” survival rate of 8.5 months, with no significant difference among treatment types, and allo-HCT was the only variable associated with improved survival.The authors also report on the “better long-term outcomes” when allo-HCT was performed during Complete Remission 1 (CR1) in previous observations. They acknowledge the limitations of their retrospective analysis, including selection bias, data heterogeneity from participating institutions, and the lack of complete molecular data prior to allo-HCT that might have influenced the results. Nevertheless, the findings are encouraging and suggest that allo-HCT improves long-term outcomes in this poor prognostic disease, where effective therapies remain limited.“In summary, this study reported improved survival when allo-HTC was performed in CR1 versus after later lines of therapy.”DOI - https://doi.org/10.18632/oncotarget.28652Correspondence to - Talha Badar - badar.talha@mayo.eduVideo short - https://www.youtube.com/watch?v=OQue9gbqsxESign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28652Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, AML, TP53 mutation, allogeneic stem cell transplantAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
While there have been significant improvements in breast cancer detection and treatment, the outlook for metastatic breast cancer remains bleak, with only a 30% five-year survival rate. This is largely due to existing therapies’ inability to effectively target the unique characteristics of metastatic cells. One key factor in metastasis is miR-10b, a small noncoding RNA known to influence cancer cell invasion, migration, viability, and proliferation.In their paper, researchers Alan Halim, Nasreen Al-Qadi, Elizabeth Kenyon, Kayla N. Conner, Sujan Kumar Mondal, Zdravka Medarova, and Anna Moore from Michigan State University’s Precision Health Program, College of Human Medicine, and College of Veterinary Medicine, and Transcode Therapeutics Inc. in Newton, Massachusetts, shared findings showing that inhibiting miR-10b impairs breast cancer cell stemness. Their research paper, entitled, “Inhibition of miR-10b treats metastatic breast cancer by targeting stem cell-like properties” was published in Volume 15 of Oncotarget on August 26, 2024.Full blog - https://www.oncotarget.org/2024/10/11/targeting-stem-cell-like-traits-how-mir-10b-inhibition-treats-metastatic-breast-cancer/Research DOI - https://doi.org/10.18632/oncotarget.28641Correspondence to - Anna Moore - moorea57@msu.eduVideo short - https://www.youtube.com/watch?v=BtaZd_iV8dISign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28641Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, breast cancer, metastasis, stem-like cells, nanoparticle, miR-10bAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- October 9, 2024 – A new #review was #published in Oncotarget's Volume 15 on September 30, 2024, entitled, “Zika virus and brain cancer: Can Zika be an effective treatment for brain cancer? A systematic review.”As highlighted in the introduction of this review, many studies have identified oncolytic viruses as a promising new class of therapeutic agents for central nervous system (CNS) tumors, particularly glioblastomas (GBM). Zika virus (ZIKV) proteins, specifically targeting certain stem cells, have shown promising results in both in vitro and animal model studies.In their review, researchers Mateus Gonçalves de Sena Barbosa, Beatriz Rodrigues Messias, Rafael Trindade Tatit, Maycon Cristian Gomes de Paula, Valdecir Boeno Spenazato Júnior, Maria Gabriella Borges Braga, Caio Vinícius Marcolino Santos, Luiza D'Ottaviano Cobos, Vinícius Otávio da Silva, Eberval Gadelha Figueiredo, Nicollas Nunes Rabelo, and Bipin Chaurasia from Atenas University Center, Passos; University of Israelita de Ciências da Saúde Albert Einstein; University of Sapucaí Valley; Atenas University Center, Sete Lagoas; Nove de Julho University, Campus Vergueiro; José do Rosário Vellano University, Alfenas; School of Medicine-University of São Paulo (FMUSP), Hospital das Clínicas/FMUSP; and Neurosurgery Clinic in Birgunj, evaluated the efficacy and safety of using ZIKV for treating CNS tumors. Data from in vivo studies were extracted and assessed for bias using the Robins-I tool, evaluating factors such as selection, performance, detection, attrition, and reporting bias.The 14 studies demonstrated that ZIKV reduced cell viability, inhibited the growth and proliferation of glioma stem cells (GSCs), and decreased Bcl2 expression, potentially enhancing chemotherapy and radiotherapy effects. ZIKV caused cytopathic effects, induced tumor cell damage, showed oncolytic properties, and selectively killed GSCs safely. This ultimately led to significant tumor remission and improved long-term survival through an enhanced T-cell response.“Although current evidence suggests ZIKV as a promising treatment for CNS tumors and may improve survival when combined with surgery and radiotherapy.”DOI - https://doi.org/10.18632/oncotarget.28647Correspondence to - Bipin Chaurasia - trozexa@gmail.comVideo short - https://www.youtube.com/watch?v=JINORGdqAO4Sign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28647Subscribe for free publication alerts from Oncotarget: https://www.oncotarget.com/subscribe/Keywords - cancer, Zika, neurotropism, glioblastoma, glioma, brain tumorAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
Oncotarget #published this #editorial on September 30, 2024, in Volume 15, entitled “Lessons from the ACDC-RP trial: Clinical trial design for radical prostatectomy neoadjuvant therapy trials” by Rashid K. Sayyid and Neil E. Fleshner from the Division of Urologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.DOI - https://doi.org/10.18632/oncotarget.28648Correspondence to - Rashid K. Sayyid - rksayyid@gmail.comVideo short - https://www.youtube.com/watch?v=APkPoTlXBWYSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28648Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, clinical trial, prostatic neoplasms, neoadjuvant therapy, chemotherapy; androgen receptor agonistAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
Macrophage Migration Inhibitory Factor (MIF) and its homolog D-dopachrome Tautomerase (DDT) have been implicated as drivers of tumor progression in various cancers. Recent evidence suggests that MIF could be a therapeutic target in immune checkpoint inhibition (ICI) resistant melanomas; however, clinical evidence for MIF, and particularly for DDT, remains limited.Researchers Caroline Naomi Valdez, Gabriela Athziri Sánchez-Zuno, Lais Osmani, Wael Ibrahim, Anjela Galan, Antonietta Bacchiocchi, Ruth Halaban, Rajan P. Kulkarni, Insoo Kang, Richard Bucala, and Thuy Tran from Yale University; Oregon Health and Science University; Cancer Early Detection Advanced Research Center (CEDAR); and the Department of Veterans Affairs Portland Health Care System analyzed 97 patients treated at Yale for melanoma between 2002–2020. Their research paper was published in Oncotarget’s Volume 15 on July 19, 2024, entitled, “Prognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma.”Full blog - https://www.oncotarget.org/2024/08/28/key-roles-of-mif-ddt-and-cd74-in-melanoma-prognosis-and-therapy/Paper DOI - https://doi.org/10.18632/oncotarget.28615Correspondence to - Thuy Tran - thuy.tran@yale.eduVideo short - https://www.youtube.com/watch?v=ULlzscn0PvQSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28615Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, MIF, DDT, melanoma, immune checkpoint inhibition, cancer transcriptomicsAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- August 28, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on August 26, 2024, entitled, “Inhibition of miR-10b treats metastatic breast cancer by targeting stem cell-like properties.”As stated within the Abstract of the paper, despite advances in breast cancer screening and treatment, the prognosis for metastatic disease remains dismal, with only a 30% five-year survival rate. This poor outcome is largely due to the failure of current therapeutics to target the unique properties of metastatic cells. One of the key drivers of metastasis is miR-10b, a small noncoding RNA implicated in cancer cell invasion, migration, viability, and proliferation. Researchers Alan Halim, Nasreen Al-Qadi, Elizabeth Kenyon, Kayla N. Conner, Sujan Kumar Mondal, Zdravka Medarova, and Anna Moore from Michigan State University’s Precision Health Program, College of Human Medicine, and College of Veterinary Medicine, and Transcode Therapeutics Inc. in Newton, Massachusetts, provide transcriptional evidence that inhibiting miR-10b with MN-anti-miR10b—a nanodrug designed to deliver anti-miR-10b antisense oligomers to cancer cells—activates developmental processes in cancer cells. They observed increased miR-10b expression in stem-like cancer cells.In mouse models of metastatic triple-negative breast cancer, MN-anti-miR10b has been shown to prevent the onset of metastasis and eliminate existing metastases when combined with chemotherapy, even after treatment has been discontinued."Our results demonstrate that inhibition of miR-10b using MN-anti-miR10b decreases the stemness of breast cancer cells, supporting dedifferentiation as a mechanism through which the nanodrug may function as a therapy."DOI - https://doi.org/10.18632/oncotarget.28641Correspondence to - Anna Moore - moorea57@msu.eduVideo short - https://www.youtube.com/watch?v=BtaZd_iV8dISign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28641Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, breast cancer, metastasis, stem-like cells, nanoparticle, miR-10bAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- August 27, 2024 – A new #editorial was #published in Oncotarget's Volume 15 on August 26, 2024, entitled, “Artificial intelligence: A transformative tool in precision oncology.”Artificial intelligence (AI) is revolutionizing society and healthcare, opening new possibilities for precision medicine. In oncology, immunotherapy (IO) has similarly transformed cancer treatment with novel therapeutic mechanisms, but it has also introduced atypical response patterns that challenge traditional evaluation methods.In this editorial, researchers Jeremy McGale, Matthew J. Liao, Egesta Lopci, Aurélien Marabelle, and Laurent Dercle from the Department of Radiology at Columbia University in New York, explore AI's role in addressing these challenges. They focus on the development of new biomarkers for precise disease characterization, particularly those using imaging for the early response assessment of cancer patients treated with IO.Additionally, the researchers highlight a comprehensive review that applied AI/radiomics to cross-sectional imaging (PET, CT, MRI) showcasing the current landscape in IO treatment. They also determined that of 87 relevant studies, most utilized algorithms to predict treatment response or prognosticate survival at predetermined time points.“In conclusion, although AI/Radiomics in IO is a rapidly advancing field, there remains significant room for improvement.”DOI - https://doi.org/10.18632/oncotarget.28639Correspondence to - Jeremy McGale - jm4782@cumc.columbia.edu, and Laurent Dercle - ld2752@cumc.columbia.eduVideo short - https://www.youtube.com/watch?v=FyZVKeUaUOsSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28639Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, immunotherapy, oncology, artificial intelligence, radiomics, lactate, dehydrogenase, PET, MRI, CT, SPECTAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- August 26, 2024 – A new #editorial was #published in Oncotarget's Volume 15 on July 10, 2024, entitled, “Genotype matters: Personalized screening recommendations for germline CHEK2 variants.”Recognized as a moderate-risk gene, CHEK2—responsible for encoding the CHK2 protein, which plays a crucial role in the repair of DNA double-strand breaks—is associated with a 20–40% lifetime risk of breast cancer (BC) by age 85. While CHEK2 pathogenic variants (PVs) were previously linked to an increased risk of colorectal cancer (CRC), two recent studies have not observed this association.In their recent work, researchers Adela Rodriguez Hernandez, Rochelle Scheib, Judy E. Garber, Huma Q. Rana and Brittany L. Bychkovsky from Dana-Farber Cancer Institute and Harvard Medical School in Boston, found that a CHEK2 PV does not increase the CRC risk compared with controls (odds ratio 0.62 (0.51–0.76), p < .001).The cancer risks associated with CHEK2 PVs vary depending on the variant type, and risk management strategies should reflect this variability. The CHEK2 c.1100del is the most studied truncating variant and has been crucial to our understanding of the cancer phenotype. Cancer risks seem to be higher with truncating variants compared to missense variants.“In our study, we postulated that these differences were driven by three common low-risk (LR) missense variants: p.I157T, p.S428F, and p.T476M, all of which have a BC odds ratio of <1.4.” In summary, CHEK2 is recognized as a moderate-risk gene for breast cancer. Further large-scale, prospective studies are needed to clarify its potential associations with prostate, kidney, and thyroid cancers, as well as to establish appropriate screening measures.DOI - https://doi.org/10.18632/oncotarget.28604Correspondence to - Brittany L. Bychkovsky - brittany_bychkovsky@dfci.harvard.eduVideo short - https://www.youtube.com/watch?v=KYHCdGz8c3ISign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28604Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, CHEK2, pathogenic or likely pathogenic variants, germlineAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- August 21, 2024 – A new #editorial was #published in Oncotarget's Volume 15 on July 17, 2024, entitled, “Strategies to disrupt NKG2A:HLA-E interactions for improved anti-cancer immunity.”Two studies using CRISPR screens in cancer cells identified HLA-E as a critical negative regulator of NK cell interactions with cancer cells. Consistent with this, IFNγ signaling was associated with NK cell resistance due to increased STAT1 activation and enhanced HLA-E expression. This effect is also evident in the murine homolog of HLA-E, Qa-1b, which was upregulated by inflammatory signals across all cell types tested.In addition to inflammatory signals, researchers Jack G. Fisher, Lara V. Graham, and Matthew D. Blunt from Clinical and Experimental Sciences, Faculty of Medicine at the University of Southampton, UK, recently demonstrated that surface expression of HLA-E is increased by lymph node-associated signals IL-4 and CD40L on primary chronic lymphocytic leukaemia (CLL) cells.Additionally, two recent studies have shown that HLA-E can protect circulating tumor cells from NK cell lysis via NKG2A, suggesting that targeting the NKG2A axis could be a promising strategy for preventing metastasis in solid tumors.“In conclusion, there is strong preclinical evidence that disruption of NKG2A interactions with HLA-E can stimulate both NK cell and cytotoxic T cell effector functions against cancer.”DOI - https://doi.org/10.18632/oncotarget.28610Correspondence to - Matthew D. Blunt - m.d.blunt@soton.ac.ukVideo short - https://www.youtube.com/watch?v=iQREIa-RToUSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28610Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, Natural killer (NK) cells, immunotherapy, NKG2A, immune checkpoint blockade, HLA-EAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- August 19, 2024 – A new #review was #published in Oncotarget's Volume 15 on August 14, 2024, entitled, “The gut barrier as a gatekeeper in colorectal cancer treatment.”Colorectal cancer (CRC) is highly prevalent and a major cause of cancer-related deaths worldwide. The primary curative treatment for CRC is surgical resection of the affected bowel segment. However, postoperative complications often include a weakened gut barrier and the dissemination of bacterial proinflammatory lipopolysaccharides.Researchers Roy Hajjar, Carole Richard, and Manuela M. Santos from Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Québec; Centre hospitalier de l’Université de Montréal (CHUM), Québec; Université de Montréal, Québec; and Institut du cancer de Montréal, Québec, discuss how gut microbiota and microbial metabolites regulate basal inflammation levels in the gut and the healing process of the bowel after surgery.“We and others have shown in the last few years that gut microbiota influences the healing process of the bowel and the restoration of the gut barrier after surgery.”The researchers further elaborate on the restoration of gut barrier function in CRC patients and how this potentially impacts the dissemination and implantation of CRC cells in extracolonic tissues, thereby contributing to worse survival outcomes after surgery.“Based on our recent work, we believe that weakened gut barrier function, namely due to poor healing after surgery, leads to persistent systemic low-grade inflammation and a higher risk of local and systemic cancer recurrence.”DOI - https://doi.org/10.18632/oncotarget.28634Correspondence to - Roy Hajjar - roy.hajjar@umontreal.caVideo short - https://www.youtube.com/watch?v=HgWx_11K6KwSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28634Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, colorectal cancer, gut microbiome, gut barrier, colorectal surgery, anastomotic leakAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- August 15, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on August 14, 2024, entitled, “A nanobody against the V-ATPase c subunit inhibits metastasis of 4T1-12B breast tumor cells to lung in mice.”The vacuolar H+-ATPase (V-ATPase) is an ATP-dependent proton pump that functions to control the pH of intracellular compartments as well as to transport protons across the plasma membrane of various cell types, including cancer cells. Researchers Zhen Li, Mohammed A. Alshagawi, Rebecca A. Oot, Mariam K. Alamoudi, Kevin Su, Wenhui Li, Michael P. Collins, Stephan Wilkens, and Michael Forgac from Tufts University School of Medicine; Tufts University; Dana Farber Cancer Institute, Harvard Medical School; University of Minnesota School of Medicine; Prince Sattam Bin Abdulaziz University; Korro Bio; SUNY Upstate Medical University; and Foghorn Therapeutics, have previously shown that selective inhibition of plasma membrane V-ATPases in breast tumor cells inhibits the invasion of these cells in vitro. They have now developed a nanobody directed against an extracellular epitope of the mouse V-ATPase c subunit.“We show that treatment of 4T1-12B mouse breast cancer cells with this nanobody inhibits V-ATPase-dependent acidification of the media and invasion of these cells in vitro.”The research team further found that injecting this nanobody into mice implanted with 4T1-12B cells orthotopically in the mammary fat pad inhibited the metastasis of tumor cells to the lungs.“In conclusion, our results indicate that a nanobody directed against an extracellular epitope expressed on the surface of the V-ATPase is able to inhibit activity of cell surface V-ATPases in 4T1-12B breast cancer cells, inhibit in vitro invasion of these cells and inhibit metastasis of these cells to lung following their implantation in the mammary fat pad of mice.”DOI - https://doi.org/10.18632/oncotarget.28638Correspondence to - Michael Forgac - michael.forgac@tufts.eduVideo short - https://www.youtube.com/watch?v=4eLGqvSfAggSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28638Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, vacuolar ATPase, breast cancer, invasion, tumor metastasis, tumor growthAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- August 14, 2024 – A new #casereport was #published in Oncotarget's Volume 15 on July 17, 2024, entitled, “Rapid but nondurable response of a BRAF exon 15 double-mutated spindle cell sarcoma to a combination of BRAF and MEK inhibitors.”As noted in the introduction of the Abstract, the BRAF V600E substitution predicts a cancer's sensitivity to BRAF inhibitor therapy, though the mutation is rarely found in soft-tissue sarcomas.Researchers Kseniya Sinichenkova, Iliya Sidorov, Nataliya Kriventsova, Dmitriy Konovalov, Ruslan Abasov, Nataliya Usman, Alexander Karachunskiy, Galina Novichkova, Dmitriy Litvinov, and Alexander Druy from the Dmitriy Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology (Ministry of Healthcare of Russian Federation) and the Research Institute of Medical Cell Technologies in Yekaterinburg, Russia, describe a case of undifferentiated spindle cell sarcoma that exhibited primary insensitivity to standard chemotherapy and a pronounced but non-sustained response to BRAF/MEK inhibitors at recurrence.The case presentation involved a 13-year-old girl that was diagnosed with low-grade spindle cell sarcoma of pelvic localization, BRAF exon 15 double-mutated: c.1799T>A p.V600E and c.1819T>A p.S607T in cis-position. “This is the first report of spindle cell sarcoma BRAF V600E/S607T double-mutated, responding to a combination of B-Raf and MEK inhibitors.”DOI - https://doi.org/10.18632/oncotarget.28606Correspondence to - Kseniya Sinichenkova - ksinichenkova@gmail.comVideo short - https://www.youtube.com/watch?v=QWEAaaixPxESign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28606Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, undifferentiated sarcoma, BRAF V600E mutation, low grade spindle cell sarcoma, abdominal cocoonAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- August 12, 2024 – A new research perspective was published in Oncotarget's Volume 15 on July 16, 2024, entitled, “Targeting the multifaceted BRAF in cancer: New directions.”In cancer patients, BRAF-targeting precision therapeutics are effective against Class I BRAF alterations (p.V600 hotspot mutations) in tumors such as melanoma, thyroid cancer, and colorectal cancer. However, numerous non-Class I BRAF inhibitors are also in development and have been explored in various cancers.Researchers Eamon Toye, Alexander Chehrazi-Raffle, Justin Hwang, and Emmanuel S. Antonarakis from the Masonic Cancer Center, University of Minnesota-Twin Cities, Department of Medicine, University of Minnesota-Twin Cities, Perelman School of Medicine, University of Pennsylvania, and the City of Hope Comprehensive Cancer Center in Duarte, California, discuss the diverse forms of BRAF alterations found in human cancers and the strategies used to inhibit them in patients with cancers of various origins.As part of their conclusion, the researchers highlighted that Class I BRAF inhibitors represent a landmark achievement in precision oncology, as demonstrated by the recent tissue-agnostic FDA approval of dabrafenib/trametinib for patients with metastatic BRAF p.V600E-mutant solid tumors. Additionally, the accelerated approval of tovorafenib for patients with relapsed/refractory BRAF-altered pediatric low-grade glioma underscores the therapeutic potential of this and other next-generation strategies targeting aberrant MAPK signaling.DOI - https://doi.org/10.18632/oncotarget.28612Correspondence to - Emmanuel S. Antonarakis - anton401@umn.edu, and Justin Hwang - jhwang@umn.eduVideo short - https://www.youtube.com/watch?v=3dRWRvOnsscSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28612Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, BRAF, MAPK, pan-cancer, precision oncology, genomicsAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
In this research paper, researchers demonstrate a promising new treatment option for refractory metastatic gastrointestinal cancers using a combination of two FDA-approved drugs.Researchers Jun Zhang, Lanlan Zhou, Shuai Zhao, and Wafik S. El-Deiry from Fox Chase Cancer Center and Brown University explore the potential of combining TAS102 (trifluridine/tipiracil) and regorafenib as a treatment option for gastrointestinal (GI) cancers. Their research paper, published in Oncotarget’s Volume 15 on July 2, 2024, is entitled, “Regorafenib synergizes with TAS102 against multiple gastrointestinal cancers and overcomes cancer stemness, trifluridine-induced angiogenesis, ERK1/2 and STAT3 signaling regardless of KRAS or BRAF mutational status.”The StudyThe combination of two FDA-approved drugs, TAS102 and regorafenib, has shown promising results in preclinical studies. TAS102 is an oral formulation consisting of trifluridine (FTD) and tipiracil hydrochloride (TPI). It has been approved by the US FDA for the treatment of refractory metastatic colorectal cancer and metastatic gastric cancer. Regorafenib is a multi-target tyrosine kinase inhibitor that inhibits tumor angiogenesis and cell proliferation and is approved for the treatment of gastrointestinal cancers.Recent studies have shown that TAS102, in combination with regorafenib, can lead to improved survival and restrict tumor progression. The combination therapy has been found effective in multiple gastrointestinal cancer cell lines, including colorectal, gastric, and pancreatic cancers.Full blog - https://www.oncotarget.org/2024/08/09/combining-regorafenib-and-tas102-to-target-gastrointestinal-cancers-and-overcome-cancer-stemness/Paper DOI - https://doi.org/10.18632/oncotarget.28602Correspondence to - Wafik S. El-Deiry - wafik@brown.eduVideo short - https://www.youtube.com/watch?v=tuEmJTkyyGQSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28602Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, TAS102, regorafenib, ERK1/2, angiogenesis, microvessel densityAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- August 8, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on August 5, 2024, entitled, “Chemical complementarity of tumor resident, T-cell receptor CDR3s and renalase-1 correlates with increased melanoma survival.”As mentioned in the Abstract of this study, overexpression of the secretory protein renalase-1 negatively impacts the survival of melanoma and pancreatic cancer patients, while inhibition of renalase-1 signaling drives tumor rejection by promoting T-cell activation. Thus, researchers Saif Zaman, Fred S. Gorelick, Andrea Chrobrutskiy, Boris I. Chobrutskiy, Gary V. Desir, and George Blanck from Yale School of Medicine, Veteran’s Administration Healthcare System, Oregon Health and Science University Hospital, Morsani College of Medicine, and H. Lee Moffitt Cancer Center and Research Institute, investigated the chemical complementarity between melanoma-resident, T-cell receptor (TCR) complementarity-determining region 3 (CDR3) amino acid sequences (AAs) and the renalase-1 protein.“In this study, we asked whether the RNLS protein could potentially be a tumor antigen by examining chemical complementarity between melanoma tumor-resident TCR CDR3s and the AA sequence of RNLS.”The results suggest that there could be biologically relevant antigenic interaction between RNLS epitopes and T-cell receptors (TCRs).“We hypothesize that RNLS protein could be recognized by TCRs, leading to local immune responses against melanoma, similar to what we have previously demonstrated with wildtype cancer antigens in the melanoma and glioblastoma settings.”DOI - https://doi.org/10.18632/oncotarget.28633Correspondence to - George Blanck - gblanck@usf.eduVideo short - https://www.youtube.com/watch?v=p3X9IgPQFJwSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28633Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, RNLS, melanoma, T-cell receptor CDR3s, chemical complementarityAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - August 7, 2024 – A new #editorial paper was #published in Oncotarget's Volume 15 on July 12, 2024, entitled, “How to deal with runaway metastatic disease?”In this new editorial, Justine Paris and Guilhem Bousquet from Université Paris Cité, Université Sorbonne Paris Nord, and APHP, Hôpital Avicenne, Oncologie médical, discussed how their research team have shown that PROM2 is a predictive biomarker of distant metastases and shorter survival among patients with stage III melanomas. More recently, in a large preclinical study using cancer cell lines and various mouse models of human melanomas, the researchers also demonstrated that the runaway metastatic process is closely linked to PROM2 overexpression, through the increase of epithelial-to-mesenchymal transition (EMT) marker expression and ferroptosis resistance. “We report two critical findings: (i) these findings, initially observed in melanoma, have also been confirmed in renal and breast cancers; (ii) we successfully implemented an original in vivo model of metastatic runaway in order to mimic what occurs in patients.”DOI - https://doi.org/10.18632/oncotarget.28609Correspondence to - Guilhem Bousquet - guilhem.bousquet@aphp.frVideo short - https://www.youtube.com/watch?v=PQr3Hb97BrwSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28609Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, metastatic disease, PROM2, biomarker, tumor growth modelsAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- August 5, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on July 12, 2024, entitled, “INT-1B3, an LNP formulated miR-193a-3p mimic, promotes anti-tumor immunity by enhancing T cell mediated immune responses via modulation of the tumor microenvironment and induction of immunogenic cell death.”In this study, researchers Chantal L. Duurland, Thijs de Gunst, Harm C. den Boer, Marion T.J. van den Bosch, Bryony J. Telford, Rogier M. Vos, Xiaolei Xie, Mingfa Zang, Fang Wang, Yingying Shao, Xiaoyu An, Jingjing Wang, Jie Cai, Ludovic Bourré, Laurens A.H. van Pinxteren, Roel Q.J. Schaapveld, Michel Janicot, and Sanaz Yahyanejad from InteRNA Technologies BV, Utrecht, The Netherlands, and Crown Bioscience Inc., in San Diego, examined the effect of their lipid nanoparticle (LNP) formulated, chemically modified, synthetic miR-193a-3p mimic (INT-1B3) on anti-tumor immunity.“In this study, we examined the effect of our lipid nanoparticle (LNP) formulated, chemically modified, synthetic miR-193a-3p mimic (INT-1B3) on animal survival, tumor microenvironment (TME) and induction of anti-tumor immune responses.”The data presented within the study demonstrates for the first time that miR-193a-3p induces long-term immunity against tumor development via modulation of the tumor microenvironment and induction of immunogenic cell death.Additionally, the data show that systemic administration of INT-1B3 to 4T1 and H22 tumor bearing immunocompetent mice prolonged animal survival by reducing metastasis compared to phosphate buffered saline (PBS) or anti-programmed death (PD) 1 treatment.DOI - https://doi.org/10.18632/oncotarget.28608Correspondence to - Sanaz Yahyanejad - sanaz.yah@gmail.comVideo short - https://www.youtube.com/watch?v=pK_Bs5vMBCQSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28608Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, miR-193a-3p, microRNA mimic, T cell mediated immunity, immunogenic cell deathAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- July 26, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on July 19, 2024, entitled, “Prognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma.”Macrophage Migration Inhibitory Factor (MIF) and its homolog D-dopachrome Tautomerase (DDT) have been implicated as drivers of tumor progression across a variety of cancers. Recent evidence suggests MIF as a therapeutic target in immune checkpoint inhibition (ICI) resistant melanomas, however clinical evidence of MIF and particularly of DDT remain limited.In this new retrospective study, researchers Caroline Naomi Valdez, Gabriela Athziri Sánchez-Zuno, Lais Osmani, Wael Ibrahim, Anjela Galan, Antonietta Bacchiocchi, Ruth Halaban, Rajan P. Kulkarni, Insoo Kang, Richard Bucala, and Thuy Tran from Yale University, Oregon Health and Science University, Cancer Early Detection Advanced Research Center (CEDAR), and the Department of Veterans Affairs Portland Health Care System analyzed 97 patients treated at Yale for melanoma between 2002–2020. “Our study significantly expands on prior work by De Azevedo et al. by encompassing a larger cohort of individuals, coupled with a comprehensive approach to defining high and low MIF and DDT expression.”Bulk-RNA sequencing of patient tumor samples from the Skin Cancer SPORE Biorepository was used to evaluate for differential gene expression of MIF, DDT, CD74, and selected inflammatory markers, and gene expression was correlated with patient survival outcomes. Their findings revealed a strong correlation between MIF and DDT levels, with no statistically significant difference across common melanoma mutations and subtypes. Improved survival was associated with lower MIF and DDT levels and higher CD74:MIF and CD74:DDT levels. High CD74:DDT and CD74:MIF levels were also associated with enrichment of infiltrating inflammatory cell markers. These data suggest DDT as a novel target in immune therapy. Dual MIF and DDT blockade may provide synergistic responses in patients with melanoma, irrespective of common mutations, and may overcome ICI resistance. These markers may also provide prognostic value for further biomarker development.“Our study is the first to report survival findings in association with intratumor DDT expression and CD74:DDT expression level ratio. Thus, CD74:MIF and CD74:DDT expression ratio measurements offer promise as prognostic markers for survival outcomes and ICI response in patients with melanoma.”DOI - https://doi.org/10.18632/oncotarget.28615Correspondence to - Thuy Tran - thuy.tran@yale.eduVideo short - https://www.youtube.com/watch?v=ULlzscn0PvQSubscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, MIF, DDT, melanoma, immune checkpoint inhibition, cancer transcriptomicsAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
In the ever-evolving quest for effective cancer treatments, researchers are continuously exploring innovative combinatorial approaches that exploit the vulnerabilities of malignant cells. In a new study, researchers Benigno C. Valdez, Apostolia M. Tsimberidou, Bin Yuan, Yago Nieto, Mehmet A. Baysal, Abhijit Chakraborty, Clark R. Andersen, and Borje S. Andersson from The University of Texas MD Anderson Cancer Center unveiled a promising synergistic strategy for combating pancreatic cancer (a cancer known for its resistance to conventional therapies). On June 3, 2024, their research paper was published in Oncotarget’s Volume 15, entitled, “Synergistic cytotoxicity of histone deacetylase and poly-ADP ribose polymerase inhibitors and decitabine in pancreatic cancer cells: Implications for novel therapy.”Full blog - https://www.oncotarget.org/2024/07/25/novel-triple-drug-combination-to-fight-pancreatic-cancer/Research paper DOI - https://doi.org/10.18632/oncotarget.28588Correspondence to - Apostolia M. Tsimberidou - atsimber@mdanderson.orgVideo short - https://www.youtube.com/watch?v=zwZVrAsdgE8Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28588Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, decitabine, HDAC inhibitors, pancreatic cancer, PARP inhibitors, synergistic cytotoxicityAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- July 24, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on July 22, 2024, entitled, “Prevalence and impact of the KIT M541L variant in patients with mastocytosis.”Activating mutations in KIT, particularly D816V, have been associated with mastocytosis. Additionally, expression of heterozygous KIT M541L has been primarily reported in patients with pediatric mastocytosis.In this new study, researchers Luisa N. Dominguez Aldama, Eric Karlins, Xiaoping Sun, Daniel Veltri, Hirsh D. Komarow, Irina Maric, Dean D. Metcalfe, and Melody C. Carter from the National Institutes of Health examined the prevalence of this variant in pediatric and adult patients with mastocytosis (n = 100) compared to ancestry-matched 1000 genomes controls (n = 500) and patients with idiopathic anaphylaxis (n = 23). They then compared clinical symptoms and laboratory data on patients with systemic and cutaneous mastocytosis and bone marrow histopathology on a matched cohort with and without the KIT M541L variant. “We found a significant association between KIT M541L genotype and the diagnosis of mastocytosis.”Overall, the KIT M541L variant was identified in 19 individuals; the majority were diagnosed with systemic mastocytosis (89.4%) with an associated KIT D816V mutation. There were no significant differences in peripheral blood parameters between groups. Patients with mastocytosis carrying the KIT M541L variant did not demonstrate significant differences in symptomatology compared to a matched reference cohort (n = 13/81) without KIT M541L. In patients with idiopathic anaphylaxis, no significant associations were observed. “To our knowledge, this is the first case/control study to show a significant genetic association with mastocytosis at the KIT M541L locus.”DOI - https://doi.org/10.18632/oncotarget.28614Correspondence to - Melody C. Carter - mcarter@niaid.nih.govVideo short - https://www.youtube.com/watch?v=zpiBbSfkTX4Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28614Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, mastocytosis, KIT M541L, KIT D816V, adults, pediatricsAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY - July 22, 2024 – Oncotarget proudly welcomes new members to our esteemed Editorial Board, including our new Co-Editor-in-Chief, Dr. Wafik S. El-Deiry. Joining Dr. El-Deiry on Oncotarget’s Editorial Board are Dr. Trever Bivona, Dr. Phillip Buckhaults, Dr. Fred Bunz, Dr. Jonathan Chernoff, Dr. Stephen G. Chun, Dr. Nathan Dolloff, Dr. Peiwen Fei, Dr. Justin D. Lathia, Dr. Bora Lim, Dr. Jia (Jenny) Liu, Dr. Hui-Wen Lo, Dr. Emil Lou, Dr. Anirban Maitra, Dr. Ruben A. Mesa, and Dr. Yashbir Singh.To learn more about our outstanding members, please visit our Editorial Board page.In celebration of the new additions to Oncotarget’s Editorial Board, we are excited to offer a special discount of 50% on all publication fees until the end of the year. This is our way of saying thank you to our supporters! To learn about how to publish with Oncotarget, please visit our Editorial Policies page.About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- July 22, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on July 10, 2024, entitled, “Improved efficacy of pembrolizumab combined with soluble EphB4-albumin in HPV-negative EphrinB2 positive head neck squamous cell carcinoma.”Patients with relapsed or metastatic head and neck squamous cell carcinoma (HNSCC) after primary local therapy have low response rates with cetuximab, systemic chemotherapy or check point inhibitor therapy. Novel combination therapies with the potential to improve outcomes for patients with HNSCC is an area of high unmet need.In this new study, researchers Alexandra Jackovich, Barbara J. Gitlitz, Justin Wayne Wong Tiu-lim, Vinay Duddalwar, Kevin George King, Anthony B. El-Khoueiry, Jacob Stephen Thomas, Denice Tsao-Wei, David I. Quinn, Parkash S. Gill, and Jorge J. Nieva from Rutgers New Jersey Medical School and the University of Southern California conducted a phase II single-arm clinical trial of locally advanced or metastatic HNSCC patients treated with a combination of soluble EphB4-human serum albumin (sEphB4-HSA) fusion protein and pembrolizumab after platinum-based chemotherapy with up to 2 prior lines of treatment. “sEphB4-HSA in combination with pembrolizumab has a safety profile similar to what has been observed previously with no overlapping toxicity.”The primary endpoints were safety and tolerability and the primary efficacy endpoint was overall response rate (ORR). Secondary endpoints included progression free survival (PFS) and overall survival (OS). HPV status and EphrinB2 expression were evaluated for outcome.Twenty-five patients were enrolled. Median follow up was 40.4 months (range 9.8 – 40.4). There were 6 responders (ORR 24%). There were 5 responders in the 11 HPV-negative and EphrinB2 positive patients, (ORR 45%) with 2 of these patients achieving a complete response (CR). The median PFS in HPV-negative/EphrinB2 positive patients was 3.2 months (95% CI 1.1, 7.3). Median OS in HPV-negative/EphrinB2 positive patients was 10.9 months (95% CI 2.0, 13.7). Hypertension, transaminitis and fatigue were the most common toxicities.“The combination of sEphB4-HSA and pembrolizumab has a favorable toxicity profile and favorable activity particularly among HPV-negative EphrinB2 positive patients with HNSCC.”DOI - https://doi.org/10.18632/oncotarget.28605Correspondence to - Alexandra Jackovich - atj41@njms.rutgers.edu, and Jorge J. Nieva - jorge.nieva@med.usc.eduVideo short - https://www.youtube.com/watch?v=8SVmHYQigwASign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28605Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, EphrinB2, EphB4, HNSCC, pembrolizumab, HPV-negativeAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- July 19, 2024 – A new #editorial paper was #published in Oncotarget's Volume 15 on July 2, 2024, entitled, “DDX41 and its unique contribution to myeloid leukemogenesis.”In this new editorial, researcher Hirotaka Matsui from the National Cancer Center Hospital in Tokyo, Japan, and Kumamoto University discusses myeloid neoplasms. Until the early 2000s, myeloid neoplasms attributable to genetic backgrounds were considered exceedingly rare, with notable exceptions limited to those arising as components of systemic syndromes such as Fanconi anemia and Li-Fraumeni syndrome. Historically, no hematopoietic-specific tumor syndromes had been identified until 1999, when RUNX1 was implicated as the causative gene for familial platelet disorder with a predisposition to acute myeloid leukemia (AML). Subsequently, in 2004, CEBPA was recognized as another critical gene responsible for inherited AML. The subsequent advent and widespread application of comprehensive genetic analysis facilitated the identification of germline pathogenic variants in genes such as ANKRD26, ETV6, and GATA2 among patients with myeloid neoplasms that developed against a background of inherited thrombocytopenia or systemic disorders. It is now established that genetic predisposition is present in approximately 10% of myeloid neoplasms, underscoring the fact that myeloid neoplasms with a genetic background are by no means exceptional.“Among these, myeloid neoplasms caused by DDX41 variants are particularly noteworthy due to their distinct disease phenotype and pathogenesis [2].”DOI - https://doi.org/10.18632/oncotarget.28603Correspondence to - Hirotaka Matsui - hmatsui@ncc.go.jpVideo short - https://www.youtube.com/watch?v=AQXIdS1amhMSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28603Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, acute myeloid leukemia, DDX41, myelodysplastic neoplasms, myeloid neoplasms with germline predisposition, R-loopAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- July 17, 2024 – A new #editorial paper was #published in Oncotarget's Volume 15 on July 2, 2024, entitled, “Using early on-treatment circulating tumor DNA measurements as response assessment in metastatic castration resistant prostate cancer.”In this new editorial, researchers S.H. Tolmeijer, E. Boerrigter, N.P. Van Erp, and Niven Mehra from Radboud University Medical Center discuss metastatic castration resistant prostate cancer (mCRPC). mCRPC is lethal, but the number of life-prolonging systemic treatments available for mCRPC has expanded over the years. Real world data suggest that the most common first-line therapy for mCRPC was treatment with an androgen receptor pathway inhibitor (ARPI), being either enzalutamide or abiraterone, although more patients will nowadays receive ARPI and/or docetaxel already for hormone sensitive prostate cancer (HSPC). Recent clinical trial data suggest potential benefit of adding poly-ADP ribose polymerase inhibitors (PARPi) or lutetium-117-prostate-specific membrane antigen (LuPSMA) to first-line mCRPC treatment with ARPIs in a subset of patients. As these different drug classes are associated with different toxicity profiles and significant costs, it is highly important to identify which patients experience durable benefit from monotherapy ARPI and which patients would potentially benefit from treatment intensification or therapy switch.“Research by Tolmeijer et al. 2023, published in Clinical Cancer Research [13], suggests that the detection of circulating tumor DNA (ctDNA) at baseline and 4-weeks after treatment initiation can predict response durability to first-line ARPIs.”DOI - https://doi.org/10.18632/oncotarget.28599Correspondence to - Niven Mehra - niven.mehra@radboudumc.nlVideo short - https://www.youtube.com/watch?v=DTJ0vEnQ9SYSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28599Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, ctDNA, prostate cancer, liquid biopsy, biomarker, androgen receptor pathway inhibitorsAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- July 16, 2024 – A new #editorial paper was #published in Oncotarget's Volume 15 on June 20, 2024, entitled, “HER2-low and HER2-zero in breast cancer between prognosis, prediction and entity.”In this new editorial, researchers Marcus Schmidt, Hans-Anton Lehr, and Katrin Almstedt from the University Medical Center of Johannes Gutenberg University discuss HER2 in breast cancer. HER2 is a well-established prognostic and predictive factor in breast cancer, which is associated with a poor prognosis but also offers the chance of improved survival when treated with targeted therapies based on the monoclonal antibody trastuzumab, both in advanced (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.71 to 0.94, P = 0.004) and in early (HR 0.66, 95% CI 0.57 to 0.77, P < 0.00001) stages. The American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) defines HER2-positivity as either 3+ by immunohistochemistry (IHC) or 2+ with amplification by in situ hybridization (ISH). Yet, the vast majority of breast tumors are considered HER2- negative (IHC 0 or 1+ or 2+ without amplification) by these criteria, and it has until recently been accepted that HER2-negative tumors do not benefit from trastuzumab based therapy. “Now, results of randomized trials with trastuzumab-based antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan (T-DXd) have fundamentally challenged this long-held view.”DOI - https://doi.org/10.18632/oncotarget.28598Correspondence to - Marcus Schmidt - marcus.schmidt@unimedizin-mainz.deVideo short - https://www.youtube.com/watch?v=4ROlLZo82uYSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28598Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, breast cancer, HER2, HER2-low, prognostic, predictiveAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- July 15, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on June 20, 2024, entitled, “Comparison of FDG-PET/CT and CT for evaluation of tumor response to nivolumab plus ipilimumab combination therapy and prognosis prediction in patients with unresectable malignant pleural mesothelioma.”Malignant pleural mesothelioma (MPM) is an aggressive neoplasm and affected patients have low survival rates. In this new retrospective study, researchers Kazuhiro Kitajima, Kozo Kuribayashi, Toshiyuki Minami, Hiroyuki Yokoyama, Akifumi Nakamura, Masaki Hashimoto, Takashi Kijima, Seiki Hasegawa, Hayato Kaida, and Koichiro Yamakado from Hyogo Medical University and Kindai University Faculty of Medicine examined the effectiveness of fluorodeoxyglucose positron emission tomography (FDG-PET) criteria, i.e., immunotherapy-modified PET response criteria in solid tumors (imPERCIST), with morphological computed tomography (CT) criteria, i.e., modified response evaluation criteria in solid tumors (mRECIST), to evaluate patients with unresectable MPM undergoing nivolumab plus ipilimumab combination therapy as first-line treatment regarding response and prognosis prediction.“Results for malignant pleural mesothelioma (MPM) patients following first-line treatment with nivolumab plus ipilimumab obtained with immunotherapy-modified PERCIST (imPERCIST), shown by [18F] (FDG-PET/CT), and modified RECIST (mRECIST), shown by CT, were compared for response evaluation and prognosis prediction.”Twenty-six patients (23 males, 3 females; median 73.5 years) with histologically proven MPM and no curative surgery received nivolumab plus ipilimumab combination therapy. FDG-PET/CT and diagnostic CT scanning at the baseline, and after 2–4 cycles (2 in three, 3 in 17, 4 in six patients) were performed. Therapeutic response findings evaluated using imPERCIST and mRECIST were compared. PFS and OS analyses were done using log-rank and Cox methods.Results: imPERCIST indicated nine progressive metabolic disease (PMD), eight stable metabolic disease (SMD), four partial metabolic response (PMR), and five complete metabolic response (CMR) cases. mRECIST showed nine with progressive disease (PD), nine stable disease (SD), seven partial response (PR), and one complete response (CR). Although high concordance was noted (κ = 0.827), imPERCIST correctly judged a greater percentage with CMR (15.4%). Following a median 10.0 months, 15 patients showed progression and eight died from MPM. With both, progression-free survival (PFS) and overall survival (OS) were significantly longer in patients without progression (CMR/PMR/SMD, CR/PR/SD, respectively) as compared to PMD/PD patients (imPERCIST p < 0.0001 and p = 0.015, respectively; mRECIST p < 0.0001 and p = 0.015, respectively).“For unresectable MPM patient examinations, FDG-PET and CT provide accurate findings for evaluating tumor response and also prognosis prediction following first-line nivolumab plus ipilimumab immunotherapy (approximately three cycles).”DOI - https://doi.org/10.18632/oncotarget.28594Correspondence to - Kazuhiro Kitajima - kazu10041976@yahoo.co.jpVideo short - https://www.youtube.com/watch?v=7ZRTRwig60YAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com.MEDIA@IMPACTJOURNALS.COM
Positron Emission Tomography (PET) combined with Computed Tomography (CT) is a powerful imaging modality used in oncology for diagnosis, staging, and treatment monitoring. However, one limitation of PET/CT is the need for accurate attenuation correction (AC) to account for tissue density variations. Traditionally, low-dose CT scans are used for AC, but these contribute to patient radiation exposure.In a new study, researchers Kevin C. Ma, Esther Mena, Liza Lindenberg, Nathan S. Lay, Phillip Eclarinal, Deborah E. Citrin, Peter A. Pinto, Bradford J. Wood, William L. Dahut, James L. Gulley, Ravi A. Madan, Peter L. Choyke, Ismail Baris Turkbey, and Stephanie A. Harmon from the National Cancer Institute proposed an artificial intelligence (AI) tool to generate attenuation-corrected PET (AC-PET) images directly from non-attenuation-corrected PET (NAC-PET) images, reducing the reliance on CT scans. Their research paper was published in Oncotarget’s Volume 15 on May 7, 2024, entitled, “Deep learning-based whole-body PSMA PET/CT attenuation correction utilizing Pix-2-Pix GAN.”Full blog - https://www.oncotarget.org/2024/07/11/ai-for-improved-pet-ct-attenuation-correction-in-prostate-cancer-imaging/Paper DOI - https://doi.org/10.18632/oncotarget.28583Correspondence to - Stephanie A. Harmon - stephanie.harmon@nih.govVideo short - https://www.youtube.com/watch?v=0mZItCB8AtISign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28583Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, deep learning, PSMA PET, attenuation correctionAbout OncotargetOncotarget is an open-access, peer-reviewed journal that has published primarily oncology-focused research papers since 2010. These papers are available to readers (at no cost and free of subscription barriers) in a continuous publishing format at Oncotarget.com. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- July 10, 2024 – A new #editorial paper was #published in Oncotarget's Volume 15 on June 20, 2024, entitled, “Targeting ABC transporters in PDAC – past, present, or future?”In this new editorial, Cecilia Bergonzini, Elisa Giovannetti and Erik H.J. Danen from Leiden University discuss targeting ABC transporters in pancreatic ductal carcinoma (PDAC). Despite its lower incidence as compared to more common cancers such as lung or breast carcinomas, PDAC ranks as the third leading cause of cancer mortality in the US and the sixth worldwide. This is due to the fact that PDAC survival rates are among the lowest for cancer patients, around 13% in the US. ATP-binding cassette (ABC) transporters represent a family of transmembrane proteins that, using the energy from ATP hydrolysis, extrude molecules from the cytoplasm to the exterior or into vesicles. Some of these transporters have been associated with resistance to a spectrum of structurally diverse chemotherapeutic drugs, earning them the name of multidrug resistance (MDR) pumps. One of the best-characterized ABC transporters is ABCB1 (MDR1). It is physiologically expressed in tissues such as kidney, liver, pancreas, intestine, the blood-brain barrier, and more, where it exerts a protective role, by extruding xenobiotics and potentially toxic molecules. Moreover, increased ABCB1 expression in tumors has been associated with poor prognosis.“Paclitaxel is a bona fide substrate for ABCB1 [18] and ABCB1 has been implicated in paclitaxel and nab-paclitaxel resistance in multiple types of cancer [19, 20]. Could ABCB1 represent a therapeutic target in PDAC patients to suppress resistance against GnP? We have recently reported that ABCB1 can indeed play a critical role in paclitaxel resistance in PDAC cells [21].”DOI - https://doi.org/10.18632/oncotarget.28597Correspondence to - Erik H.J. Danen - e.danen@lacdr.leidenuniv.nlVideo short - https://www.youtube.com/watch?v=safa58X8NMYSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28597Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, PDAC, chemoresistance, ABCB1 About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- July 8, 2024 – A new research paper was published in Oncotarget's Volume 15 on July 2, 2024, entitled, “Regorafenib synergizes with TAS102 against multiple gastrointestinal cancers and overcomes cancer stemness, trifluridine-induced angiogenesis, ERK1/2 and STAT3 signaling regardless of KRAS or BRAF mutational status.”Single-agent TAS102 (trifluridine/tipiracil) and regorafenib are FDA-approved treatments for metastatic colorectal cancer (mCRC). Researchers previously reported that regorafenib combined with a fluoropyrimidine can delay disease progression in clinical case reports of multidrug-resistant mCRC patients. In this new study, researchers Jun Zhang, Lanlan Zhou, Shuai Zhao, and Wafik S. El-Deiry from Fox Chase Cancer Center and Brown University hypothesized that the combination of TAS102 and regorafenib may be active in CRC and other gastrointestinal (GI) cancers and may in the future provide a treatment option for patients with advanced GI cancer. “We investigated the therapeutic effect of TAS102 in combination with regorafenib in preclinical studies employing cell culture, colonosphere assays that enrich for cancer stem cells, and in vivo.”TAS102 in combination with regorafenib has synergistic activity against multiple GI cancers in vitro including colorectal and gastric cancer, but not liver cancer cells. TAS102 inhibits colonosphere formation and this effect is potentiated by regorafenib. In vivo anti-tumor effects of TAS102 plus regorafenib appear to be due to anti-proliferative effects, necrosis and angiogenesis inhibition. Growth inhibition by TAS102 plus regorafenib occurs in xenografted tumors regardless of p53, KRAS or BRAF mutations, although more potent tumor suppression was observed with wild-type p53. Regorafenib significantly inhibits TAS102-induced angiogenesis and microvessel density in xenografted tumors, as well inhibits TAS102-induced ERK1/2 activation regardless of RAS or BRAF status in vivo. TAS102 plus regorafenib is a synergistic drug combination in preclinical models of GI cancer, with regorafenib suppressing TAS102-induced increase in microvessel density and p-ERK as contributing mechanisms. “The TAS102 plus regorafenib drug combination may be further tested in gastric and other GI cancers.”DOI - https://doi.org/10.18632/oncotarget.28602Correspondence to - Wafik S. El-Deiry - wafik@brown.eduVideo short - https://www.youtube.com/watch?v=tuEmJTkyyGQSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28602Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, TAS102, regorafenib, ERK1/2, angiogenesis, microvessel densityAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- July 2, 2024 – A new editorial paper was published in Oncotarget's Volume 15 on June 20, 2024, entitled, “Genomics has more to reveal.”In this new editorial, researchers Laurène Fenwarth and Nicolas Duployez from the University of Lille and CHU Lille discuss molecular and cytogenetic analyses that are now used to identify mutations and structural variants defining distinct subtypes of acute myeloid leukemias (AML) and myelodysplastic syndromes (MDS). These genetic considerations have become essential for risk stratification and the selection of appropriate treatments, including the use of allogeneic hematopoietic stem cell transplantation. “Despite over 15 years of genomic research since the first publication of the AML genome and large studies like The Cancer Genome Atlas (TCGA) [2], around 15% of AML cases remained genetically unclassifiable with current knowledge.”Notably, several studies in both adults and children identified a subset of AML without known initiating events but particularly enriched in FLT3- ITD and WT1 mutations, and normal karyotypes with an overall unfavorable prognosis. In 2021–2022, notably thanks to advancements in bioinformatic approaches and tools, recurrent somatic tandem duplications (TD) of a portion of the UBTF gene were identified in high-risk pediatric AML cases. “With increased screenings of retrospective cohorts, the characteristics associated with this molecular alteration have since been confirmed. UBTF-TD are considered initiating events in leukemogenesis and define a distinct entity of myeloid malignancies.”DOI - https://doi.org/10.18632/oncotarget.28596Correspondence to - Nicolas Duployez - nicolas.duployez@chu-lille.frVideo short - https://www.youtube.com/watch?v=WVY_ejhr7FcSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28596Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, acute myeloid leukemia, genomics, UBTFAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- June 26, 2024 – A new research perspective was published in Oncotarget's Volume 15 on June 20, 2024, entitled, “Starving cancer cells to enhance DNA damage and immunotherapy response.”Prostate cancer (PCa) poses significant challenges in treatment, particularly when it progresses to a metastatic, castrate-resistant state. Conventional therapies, including chemotherapy, radiotherapy, and hormonal treatments, often fail due to toxicities, off-target effects, and acquired resistance. In this new research perspective, researchers Aashirwad Shahi and Dawit Kidane from Howard University define an alternative therapeutic strategy focusing on the metabolic vulnerabilities of PCa cells, specifically their reliance on non-essential amino acids such as cysteine. “In this prospective, we will rise the driving questions and potential possibilities how amino acid depletion induced oxidative stress associated DNA damage exploited for DNA repair targeted and immune checkpoint blockade therapy [...].”Using an engineered enzyme cyst(e)inase to deplete the cysteine/cystine can induce oxidative stress and DNA damage in cancer cells. This depletion elevates reactive oxygen species (ROS) levels, disrupts glutathione synthesis, and enhances DNA damage, leading to cancer cell death. The combinatorial use of cyst(e)inase with agents targeting antioxidant defenses, such as thioredoxins, further amplifies ROS accumulation and cytotoxicity in PCa cells. “Overall, this perspective provides a compressive overview of the previous work on manipulating amino acid metabolism and redox balance modulate the efficacy of DNA repair-targeted and immune checkpoint blockade therapies in prostate cancer.”DOI - https://doi.org/10.18632/oncotarget.28595Correspondence to - Dawit Kidane - dawit.kidane-mulat@howard.eduVideo short - https://www.youtube.com/watch?v=Zrj24o_-b50Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28595Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, amino acid depletion, DNA damage, DNA repair, Immunotherapy, tumor immunityAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- June 24, 2024 – A new editorial paper was published in Oncotarget's Volume 15 on June 14, 2024, entitled, “Leveraging gold nanostars for precision laser interstitial thermal therapy.”In this new editorial, researchers Aden P. Haskell-Mendoza, Ethan S. Srinivasan, Tuan Vo-Dinh and Peter E. Fecci from Duke University discuss laser interstitial thermal therapy (LITT). Over the past decade, LITT has become an important tool for the neurosurgical treatment of a variety of intracranial pathologies, including focal epilepsies, vascular malformations, and central nervous system (CNS) tumors [1]. LITT involves the minimally invasive, stereotactically-guided placement of a laser catheter into a target lesion for subsequent thermal ablation via the delivery of infrared radiation, typically at wavelengths of 980–1064 nm [1, 2]. Following transfer of the patient to a scanner, real-time magnetic resonance (MR) thermometry is employed to track tissue hyperthermal ablation. “For patients with primary and metastatic brain tumors who are suboptimal candidates for craniotomy due to clinical status, wound healing concerns, or tumor location, LITT represents a particularly favorable option for reducing tumor burden.” However, successful ablation is limited by the (1) inability to precisely sculpt heat to cover or conform to large (typically, ≥3 cm) or irregular lesions, (2) the presence of various intracranial heat sinks, including cerebrospinal fluid (CSF) spaces and blood vessels, and (3) the sensitivity of uninvolved white and gray matter structures to inadvertent thermal damage [1–3]. “To aid in the performance of more efficient, conformal, and accordingly, safe ablations, we recently developed procedures for the use of gold nanostars (GNS, Figure 1) [2]."DOI - https://doi.org/10.18632/oncotarget.28592Correspondence to - Peter E. Fecci - peter.fecci@duke.eduVideo short - https://www.youtube.com/watch?v=ZRMk0ZLjgxcSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28592Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, laser interstitial thermal therapy, gold nanostars, brain tumors, thermal ablation, immunotherapyAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
Breast cancer immunotherapy has shown promise, but its clinical efficacy remains limited, especially for hormone receptor positive (HR+)/HER2-negative breast cancer. While immune checkpoint inhibitors combined with chemotherapy have benefitted some early-stage and metastatic triple-negative breast cancer patients, HR+/HER2-negative cases have seen fewer improvements.Recent neoadjuvant trials indicate that early-stage HR+/HER2-negative breast cancers might respond better to immunotherapy strategies that amplify tumor-infiltrating lymphocytes (TILs) through dual PD-(L)1/CTLA-4 checkpoint inhibition before surgery and chemotherapy. This approach could enhance the immune response in the tumor microenvironment and improve outcomes for this challenging breast cancer subtype.Increased TILs are associated with improved neoadjuvant chemotherapy (NACT) responses across breast cancer subtypes. Recently, researchers Haven R. Garber, Sreyashi Basu, Sonali Jindal, Zhong He, Khoi Chu, Akshara Singareeka Raghavendra, Clinton Yam, Lumarie Santiago, Beatriz E. Adrada, Padmanee Sharma, Elizabeth A. Mittendorf, and Jennifer K. Litton from the University of Texas MD Anderson Cancer Center, Brigham and Women’s Hospital, Dana-Farber Brigham Cancer Center, and Harvard Medical School hypothesized that amplifying TILs via dual checkpoint blockade would enhance the response to subsequent NACT in breast tumors.Full blog - https://www.oncotarget.org/2024/06/20/impact-of-dual-immunotherapies-before-surgery-in-hr-her2-negative-breast-cancer/Paper DOI -https://doi.org/10.18632/oncotarget.28567Correspondence to - Haven R. Garber - hrgarber@mdanderson.orgVideo short - https://www.youtube.com/watch?v=PHpndZJHB_cSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28567Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, breast cancer, ER positive, immunotherapy, neoadjuvant chemotherapy, tumor microenvironmentAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- June 19, 2024 – A new research paper was published in Oncotarget's Volume 15 on June 13, 2024, entitled, “Assessment of serum tumor markers CEA, CA-125, and CA19-9 as adjuncts in non-small cell lung cancer management.”Conventional tumor markers may serve as adjuncts in non-small cell lung cancer (NSCLC) management. In this new study, researchers Scott Strum, Mark Vincent, Meghan Gipson, Eric McArthur, and Daniel Breadner from the Schulich School of Medicine and Dentistry, London Health Sciences Centre, and Royal College of Surgeons in Ireland analyzed whether three tumor markers (CEA, CA19-9, and CA-125) held associations with radiographic and clinical outcomes in NSCLC. “The aim of this retrospective study was to provide additional evidence for the clinical use of conventional serum tumor markers CEA, CA19-9, and CA-125 in NSCLC management.”It constituted a single-center study of NSCLC patients treated with systemic therapy at the London Regional Cancer Program. Serum tumor markers were analyzed for differences in radiographic responses (RECIST v1.1 or iRECIST), associations with clinical characteristics, and all-cause mortality. A total of 533 NSCLC patients were screened, of which 165 met inclusion criteria. A subset of 92 patients had paired tumor markers and radiographic scans. From the latter population, median (IQR) fold-change from nadir to progression was 2.13 (IQR 1.24–3.02; p < 0.001) for CEA, 1.46 (IQR 1.13–2.18; p < 0.001) for CA19-9, and 1.53 (IQR 0.96–2.12; p < 0.001) for CA-125. Median (IQR) fold-change from baseline to radiographic response was 0.50 (IQR 0.27, 0.95; p < 0.001) for CEA, 1.08 (IQR 0.74, 1.61; p = 0.99) for CA19-9, and 0.47 (IQR 0.18, 1.26; p = 0.008) for CA-125. “In conclusion, tumor markers are positioned to be used as adjunct tools in clinical decision making, especially for their associations with radiographic response (CEA/CA-125) or progression (CEA/CA-125/CA-19-9).”DOI - https://doi.org/10.18632/oncotarget.28566Correspondence to - Daniel Breadner - daniel.breadner@lhsc.on.caVideo short - https://www.youtube.com/watch?v=8LO-Hn0fbrgSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28566Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, tumor marker, biomarker, lung cancer; NSCLC, translational researchAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- June 18, 2024 – A new #research perspective was #published in Oncotarget's Volume 15 on June 13, 2024, entitled, “When does a melanoma metastasize? Implications for management.”In this new perspective, researchers John F. Thompson and Gabrielle J. Williams from The University of Sydney, Royal Prince Alfred Hospital, and the University of Western Australia discussed melanoma and timing treatment. Selecting which patients with clinically localized melanoma require treatment other than wide excision of the primary tumor is based on the risk or presence of metastatic disease. This in turn is linked to survival. “Knowing if and when a melanoma is likely to metastasize is therefore of great importance.” Several studies employing a range of different methodologies have suggested that many melanomas metastasize long before the primary lesion is diagnosed. Therefore, waiting for dissemination of metastatic disease to become evident before making systemic therapy available to these patients may be less effective than giving them post-operative adjuvant therapy initially if the metastatic risk is high. The identification of these high-risk patients will assist in selecting those to whom adjuvant systemic therapy can most appropriately be offered. “Further studies are required to better identify high-risk patients whose primary melanoma is likely to have already metastasized.”DOI - https://doi.org/10.18632/oncotarget.28591Correspondence to - John F. Thompson - john.thompson@melanoma.org.auVideo short - https://www.youtube.com/watch?v=1rOlvR5_6SgSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28591Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, melanoma, metastasis, time, adjuvant systemic therapy, tumor doubling timeAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- June 11, 2024 – The Ride for Roswell is one of the nation’s largest cycling events—hosted by Roswell Park Comprehensive Cancer Center—to raise awareness and funds for cancer research and patient care. This charity bike ride, based out of Buffalo, New York, has brought people together for 28 years to celebrate cancer survivors, pay tribute to lives that have been lost, and to work together to support research and find a cure.THE ORIGIN OF THE RIDEThe Ride for Roswell started in 1989 when Mitch Flynn, owner of the advertising agency Flynn & Friends, met Katherine Gioia. Katherine was a four-year-old patient battling a rare form of cancer. After Katherine’s death (less than a year after her diagnosis), Katherine’s mother, Anne Gioia, and aunt, Donna Gioia, founded the Roswell Park Alliance Foundation in her memory to raise money for cancer research and treatment. On June 29, 1996, Mitch and Alliance Foundation staff launched the first Ride for Roswell.In the 28 years since then, thanks to over 135,000 riders and thousands of volunteers, the Ride for Roswell has raised over $72 million to fund cancer research. The event has become one of the largest charity rides in the United States.THIS YEARThis year, Ride Day is on Saturday, June 22, 2024, and will once again begin at the University at Buffalo North Campus. There are nine routes to choose from, ranging from five to 100 mile distances. All riders are encouraged to check in on the Thursday or Friday before Ride Day.Learn more about The Ride, check in, and routes: www.rideforroswell.org/routes/JOIN A TEAM: TEAM OPEN ACCESSImpact Journals has been a part of this event since 2018 and continues to sponsor captain Sergei Kurenov’s peloton, Team Open Access. Team Open Access was named in honor of all open-source online medical journals, such as Oncotarget, Aging, Genes & Cancer, and Oncoscience. Sergei works at Roswell Park Comprehensive Cancer Center to create, develop, and implement innovative diagnostic and surgical pre-planning software used in cancer treatment. He has been riding in the event since 2016.“I am proud to [say] that our team is supported again by open source cancer-related scientific journals: Oncotarget and Aging! Both of these journals publish high-impact research papers of general interest and biological significance in all fields of cancer research,” Sergei said.There is still time to join Team Open Access in the Ride for Roswell. You can also support the team by giving a donation of any size. Any avenue of support you may choose to donate to the Ride for Roswell will make a difference and change lives.“Finding a cure for cancer is something we are all incredibly passionate about, and we are so thankful and grateful for your support. Together, we can make a difference!” Sergei said. “Thank you so much for your donations, your support, and well wishes!”Visit the Open Access team page to join or donate today:give.roswellpark.org/site/TR/Specia…eam&fr_id=1940For media requests, please contact media@impactjournals.com.
In the relentless battle against non-small cell lung cancer (NSCLC) driven by epidermal growth factor receptor (EGFR) mutations, the development of resistance has long been a formidable obstacle. Historically, first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) like gefitinib, erlotinib, afatinib, and dacomitinib have faced a significant hurdle: the emergence of the T790M point mutation in approximately 50% of patients, rendering the tumor resistant to these therapies.This resistance stems from a sobering reality – before treatment, a small subset of cancer cells already harbor the T790M mutation, conferring no selective advantage initially. However, once treatment commences, these rare mutated cells proliferate selectively, eventually dominating the tumor population and diminishing the effectiveness of first- and second-generation TKIs.Full blog - https://www.oncotarget.org/2024/06/06/dr-blagosklonnys-strategy-from-osimertinib-to-preemptive-combinations/Paper DOI - https://doi.org/10.18632/oncotarget.28569Correspondence to - Mikhail V. Blagosklonny - Blagosklonny@oncotarget.com, Blagosklonny@rapalogs.comVideo short - https://www.youtube.com/watch?v=UO5BGLIggTESign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28569Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, lung cancer, NSCLC, EGFR, resistance, afatinib, gefitinib, capmatinibAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- June 5, 2024 – A new research paper was published in Oncotarget's Volume 15 on June 3, 2024, entitled, “Synergistic cytotoxicity of histone deacetylase and poly-ADP ribose polymerase inhibitors and decitabine in pancreatic cancer cells: Implications for novel therapy.”Histone deacetylase inhibitors (HDACi) can modulate the acetylation status of proteins, influencing the genomic instability exhibited by cancer cells. Poly (ADP ribose) polymerase (PARP) inhibitors (PARPi) have a direct effect on protein poly (ADP-ribosyl)ation, which is important for DNA repair. Decitabine is a nucleoside cytidine analogue, which when phosphorylated gets incorporated into the growing DNA strand, inhibiting methylation and inducing DNA damage by inactivating and trapping DNA methyltransferase on the DNA, thereby activating transcriptionally silenced DNA loci.In this new study, researchers Benigno C. Valdez, Apostolia M. Tsimberidou, Bin Yuan, Yago Nieto, Mehmet A. Baysal, Abhijit Chakraborty, Clark R. Andersen, and Borje S. Andersson from The University of Texas MD Anderson Cancer Center explored various combinations of HDACi and PARPi +/− decitabine (hypomethylating agent) in pancreatic cancer cell lines BxPC-3 and PL45 (wild-type BRCA1 and BRCA2) and Capan-1 (mutated BRCA2). “[...] we explored various combinations of HDACis and PARPis, with or without decitabine, in pancreatic cancer cell lines.”The combination of HDACi (panobinostat or vorinostat) with PARPi (talazoparib or olaparib) resulted in synergistic cytotoxicity in all cell lines tested. The addition of decitabine further increased the synergistic cytotoxicity noted with HDACi and PARPi, triggering apoptosis (evidenced by increased cleavage of caspase 3 and PARP1). The 3-drug combination treatments (vorinostat, talazoparib, and decitabine; vorinostat, olaparib, and decitabine; panobinostat, talazoparib, and decitabine; panobinostat, olaparib, and decitabine) induced more DNA damage (increased phosphorylation of histone 2AX) than the individual drugs and impaired the DNA repair pathways (decreased levels of ATM, BRCA1, and ATRX proteins). The 3-drug combinations also altered the epigenetic regulation of gene expression (NuRD complex subunits, reduced levels). “This is the first study to demonstrate synergistic interactions between the aforementioned agents in pancreatic cancer cell lines and provides preclinical data to design individualized therapeutic approaches with the potential to improve pancreatic cancer treatment outcomes.”DOI - https://doi.org/10.18632/oncotarget.28588Correspondence to - Apostolia M. Tsimberidou - atsimber@mdanderson.orgSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28588Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- June 4, 2024 – A new research perspective was published in Oncotarget's Volume 15 on June 3, 2024, entitled, “Bruton’s tyrosine kinase inhibitor-related cardiotoxicity: The quest for predictive biomarkers and improved risk stratification.”In this new perspective, researchers Jai N. Patel, Jai Singh, and Nilanjan Ghosh from Atrium Health discuss Ibrutinib — the first Bruton's tyrosine kinase (BTK) inhibitor approved for the treatment of patients with chronic lymphocytic leukemia (CLL). “While producing durable responses and prolonging survival, roughly 20–25% of patients experience dose limiting side effects, mostly consisting of cardiovascular toxicities like severe hypertension and atrial fibrillation.”While clinical predictors of BTK inhibitor-related cardiotoxicity have been proposed and may aid in risk stratification, there is no routine risk model used in clinical practice today to identify patients at highest risk. A recent study investigating genetic predictors of ibrutinib-related cardiotoxicity found that single nucleotide polymorphisms in KCNQ1 and GATA4 were significantly associated with cardiotoxic events. If replicated in larger studies, these biomarkers may improve risk stratification in combination with clinical factors. “A clinicogenomic risk model may aid in identifying patients at highest risk of developing BTK inhibitor-related cardiotoxicity in which further risk mitigation strategies may be explored.”DOI - https://doi.org/10.18632/oncotarget.28589Correspondence to - Nilanjan Ghosh - nilanjan.ghosh@atriumhealth.orgSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28589Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, BTK inhibitor, cardiotoxicity, biomarkers, risk, geneticsAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
Dr. Benoit Chabot from Université de Sherbrooke in Quebec, CA, discusses a research paper he co-authored that was published by Oncotarget in Volume 15, entitled, “The anticancer potential of the CLK kinases inhibitors 1C8 and GPS167 revealed by their impact on the epithelial-mesenchymal transition and the antiviral immune response.”DOI - https://doi.org/10.18632/oncotarget.28585Correspondence to - Benoit Chabot - benoit.chabot@usherbrooke.caAbstractThe diheteroarylamide-based compound 1C8 and the aminothiazole carboxamide-related compound GPS167 inhibit the CLK kinases, and affect the proliferation of a broad range of cancer cell lines. A chemogenomic screen previously performed with GPS167 revealed that the depletion of components associated with mitotic spindle assembly altered sensitivity to GPS167. Here, a similar screen performed with 1C8 also established the impact of components involved in mitotic spindle assembly. Accordingly, transcriptome analyses of cells treated with 1C8 and GPS167 indicated that the expression and RNA splicing of transcripts encoding mitotic spindle assembly components were affected. The functional relevance of the microtubule connection was confirmed by showing that subtoxic concentrations of drugs affecting mitotic spindle assembly increased sensitivity to GPS167. 1C8 and GPS167 impacted the expression and splicing of transcripts in pathways relevant to tumor progression, including MYC targets and the epithelial mesenchymal transition (EMT). Finally, 1C8 and GPS167 altered the expression and alternative splicing of transcripts involved in the antiviral immune response. Consistent with this observation, depleting the double-stranded RNA sensor DHX33 suppressed GPS167-mediated cytotoxicity on HCT116 cells. Our study uncovered molecular mechanisms through which 1C8 and GPS167 affect cancer cell proliferation as well as processes critical for metastasis.Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28585Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, CLK kinases inhibitors, EMT, antiviral immune response, microtubules, metastasisAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- May 28, 2024 – A new review paper was published in Oncotarget's Volume 15 on May 23, 2024, entitled, “The importance of integrated therapies on cancer: Silibinin, an old and new molecule.”In this new review, researchers Elisa Roca, Giuseppe Colloca, Fiorella Lombardo, Andrea Bellieni, Alessandra Cucinella, Giorgio Madonia, Licia Martinelli, Maria Elisa Damiani, Ilaria Zampieri, and Antonio Santo from Perderzoli Hospital and Fondazione Policlinico Universitario “A. Gemelli” begin their abstract by noting that the efficacy of coadjuvant molecules, in the landscape of cancer treatments, remains a focus of attention for clinical research with the aim of reducing toxicity and achieving better outcomes.“Most of the pathogenetic processes causing tumour development, neoplastic progression, ageing, and increased toxicity involve inflammation.”Inflammatory mechanisms can progress through a variety of molecular patterns. As is well known, the ageing process is determined by pathological pathways very similar and often parallel to those that cause cancer development. Among these complex mechanisms, inflammation is currently much studied and is often referred to in the geriatric field as ‘inflammaging’. In this context, treatments active in the management of inflammatory mechanisms could play a role as adjuvants to standard therapies.Among these emerging molecules, Silibinin has demonstrated its anti-inflammatory properties in different neoplastic types, also in combination with chemotherapeutic agents. Moreover, this molecule could represent a breakthrough in the management of age-related processes. Thus, Silibinin could be a valuable adjuvant to reduce drug-related toxicity and increase therapeutic potential.“For this reason, the main aim of this review is to collect and analyse data presented in the literature on the use of Silibinin, to better understand the mechanisms of the functioning of this molecule and its possible therapeutic role.”DOI - https://doi.org/10.18632/oncotarget.28587Correspondence to - Elisa Roca - elisaroca@gmail.comSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28587Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, silibinin, anti-inflammatory, inflammation, toxicity, integrated therapyAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
Upon diagnosing acute myeloid leukemia (AML), the initial step involves assessing a patient’s eligibility for intensive chemotherapy. The standard treatment protocol for newly diagnosed AML encompasses intensive chemotherapy to achieve complete remission, followed by post-remission therapy, which may include additional chemotherapy and/or stem cell transplantation. Complete response rates to this approach range from 60% to 85% in adults aged 60 or younger.While this approach has proven effective, the risk of relapse within three years of diagnosis remains a significant concern. Numerous factors contribute to the likelihood of relapse, including short duration of remission, genetic derangements, prior allogeneic transplantation, advanced age, and concomitant comorbidities. These negative prognostic factors underscore the need for continuous exploration of novel therapeutic agents, as relapse remains a formidable barrier to treatment success.In a new study, researchers Simonetta I. Gaumond, Rama Abdin, Joel Costoya, Andrew V. Schally (awarded the Nobel Prize in Physiology or Medicine in 1977), and Joaquin J. Jimenez from the University of Miami, Florida Atlantic University and Veterans Affairs Medical Center, Miami, investigated newly emerging therapies targeting drug resistance in AML. On April 8, 2024, their new research paper was published in Oncotarget’s Volume 15, entitled, “Exploring the role of GHRH antagonist MIA-602 in overcoming Doxorubicin-resistance in acute myeloid leukemia.”Full blog - https://www.oncotarget.org/2024/05/23/combating-doxorubicin-resistant-acute-myeloid-leukemia/Paper DOI - https://doi.org/10.18632/oncotarget.28579Correspondence to - Simonetta I. Gaumond - sxg1204@miami.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28579Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, leukemia, AML, resistance, growth hormone-releasing hormone, MIA-602About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- May 22, 2024 – A new research paper was published in Oncotarget's Volume 15 on May 17, 2024, entitled, “GZ17-6.02 kills PDX isolates of uveal melanoma.”In this new study, researchers Laurence Booth, Jane L. Roberts, Ivan Spasojevic, Kaitlyn C. Baker, Andrew Poklepovic, Cameron West, John M. Kirkwood, and Paul Dent from Virginia Commonwealth University, Duke University School of Medicine, Genzada Pharmaceuticals, Texas Tech University Health Sciences Center, and University of Pittsburgh Cancer Institute defined the biology of GZ17-6.02 in UM cells and in parallel determined its interaction with irreversible ERBB inhibitors (afatinib, neratinib) and with the cytotoxic agent doxorubicin. “GZ17-6.02 is a novel compound, containing the synthetically manufactured components: curcumin, harmine and isovanillin and has undergone phase I safety evaluation in cancer patients (NCT03775525).”GZ17-6.02 has undergone phase I evaluation in patients with solid tumors (NCT03775525). The RP2D is 375 mg PO BID, with an uveal melanoma patient exhibiting a 15% reduction in tumor mass for 5 months at this dose. Studies in this manuscript have defined the biology of GZ17-6.02 in PDX isolates of uveal melanoma cells. GZ17-6.02 killed uveal melanoma cells through multiple convergent signals including enhanced ATM-AMPK-mTORC1 activity, inactivation of YAP/TAZ and inactivation of eIF2α. GZ17-6.02 significantly enhanced the expression of BAP1, predictive to reduce metastasis, and reduced the levels of ERBB family RTKs, predicted to reduce growth. GZ17-6.02 interacted with doxorubicin or ERBB family inhibitors to significantly enhance tumor cell killing which was associated with greater levels of autophagosome formation and autophagic flux. Knock down of Beclin1, ATG5 or eIF2α were more protective than knock down of ATM, AMPKα, CD95 or FADD, however, over-expression of FLIP-s provided greater protection compared to knock down of CD95 or FADD. Expression of activated forms of mTOR and STAT3 significantly reduced tumor cell killing. GZ17-6.02 reduced the expression of PD-L1 in uveal melanoma cells to a similar extent as observed in cutaneous melanoma cells whereas it was less effective at enhancing the levels of MHCA. The components of GZ17-6.02 were detected in tumors using a syngeneic tumor model. “Our data support future testing GZ17-6.02 in uveal melanoma as a single agent, in combination with ERBB family inhibitors, in combination with cytotoxic drugs, or with an anti-PD1 immunotherapy.”DOI - https://doi.org/10.18632/oncotarget.28586Correspondence to - Paul Dent - paul.dent@vcuhealth.orgSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28586Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, autophagy, ER stress, GZ17-6.02, doxorubicin, afatinib, neratinibAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- May 20, 2024 – A new research paper was published in Oncotarget's Volume 15 on May 16, 2024, entitled, “The anticancer potential of the CLK kinases inhibitors 1C8 and GPS167 revealed by their impact on the epithelial-mesenchymal transition and the antiviral immune response.”The diheteroarylamide-based compound 1C8 and the aminothiazole carboxamide-related compound GPS167 inhibit the CLK kinases, and affect the proliferation of a broad range of cancer cell lines. A chemogenomic screen previously performed with GPS167 revealed that the depletion of components associated with mitotic spindle assembly altered sensitivity to GPS167. In this new study, researchers Lulzim Shkreta, Johanne Toutant, Aurélie Delannoy, David Durantel, Anna Salvetti, Sophie Ehresmann, Martin Sauvageau, Julien A. Delbrouck, Alice Gravel-Trudeau, Christian Comeau, Caroline Huard, Jasmin Coulombe-Huntington, Mike Tyers, David Grierson, Pierre-Luc Boudreault, and Benoit Chabot from Université de Sherbrooke, Université de Lyon, Institut de recherches cliniques de Montréal, Université de Montréal, and University of British Columbia a similar screen performed with 1C8 also established the impact of components involved in mitotic spindle assembly. “Accordingly, transcriptome analyses of cells treated with 1C8 and GPS167 indicated that the expression and RNA splicing of transcripts encoding mitotic spindle assembly components were affected.” The functional relevance of the microtubule connection was confirmed by showing that subtoxic concentrations of drugs affecting mitotic spindle assembly increased sensitivity to GPS167. 1C8 and GPS167 impacted the expression and splicing of transcripts in pathways relevant to tumor progression, including MYC targets and the epithelial mesenchymal transition (EMT). Finally, 1C8 and GPS167 altered the expression and alternative splicing of transcripts involved in the antiviral immune response. Consistent with this observation, depleting the double-stranded RNA sensor DHX33 suppressed GPS167-mediated cytotoxicity on HCT116 cells. “Our study uncovered molecular mechanisms through which 1C8 and GPS167 affect cancer cell proliferation as well as processes critical for metastasis."DOI - https://doi.org/10.18632/oncotarget.28585Correspondence to - Benoit Chabot - benoit.chabot@usherbrooke.caSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28585Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, CLK kinases inhibitors, EMT, antiviral immune response, microtubules, metastasisAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- May 15, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on May 14, 2024, entitled, “Cyclin D1 expression in penile cancer.”In this new study, researchers Wesliany Everton Duarte, Jaqueline Diniz Pinho, Syomara Pereira da Costa Melo, Denner Rodrigo Diniz Duarte, Juliana Martins da Guia Ribeiro do Carmo, André Salim Khayat, José Ribamar Rodrigues Calixto, Marcos Adriano Garcia Campos, Rita da Graça Carvalhal Frazão Correa, Antonio Machado Alencar Júnior, Antônio Augusto Lima Teixeira-Júnior, and Gyl Eanes Barros Silva from Federal University of Maranhão, State University of Maranhão, Federal University of Pará, São Paulo State University, and University of São Paulo analyzed the expression profile of cyclin D1 in patients with PC, and to determine possible correlations with clinical and histopathological features. “Regarding PC, however, few studies have assessed the role of cyclin D1, reinforcing the necessity for initiatives that aim to investigate its actual role in the pathophysiology of this disease. As such, the present study aimed to characterize the expression of cyclin D1 in patients with PC, and to determine possible correlations with the clinical and histopathological features of the disease.”A survey was conducted with 100 patients diagnosed with PC, who were treated at two reference hospitals in São Luís, Maranhão, Brazil, between 2013 and 2017. A review of clinical, epidemiological, and histopathological data was performed, Human Papillomavírus (HPV) DNA was detected using polymerase chain reaction (PCR) and cyclin D1 expression analysis was performed using immunohistochemical techniques. The data revealed that the absence of cyclin D1 expression was significantly associated with HPV-positive histological subtypes (p = 0.001), while its expression was associated with high-grade tumors (p = 0.014), histological subtype (p = 0.001), presence of sarcomatoid transformation (p = 0.04), and perineural invasion (p = 0.023). Patients with cyclin D1 expression exhibited lower disease-free survival compared to the cyclin D1-negative group, although the difference was not statistically significant. “The results suggest that cyclin D1 may be a potential biomarker for PC, especially for poorer prognosis.”DOI - https://doi.org/10.18632/oncotarget.28584Correspondence to - Gyl Eanes Barros Silva - gyl.silva@ufma.brSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28584Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, immunohistochemistry, biomarkers, cyclin D1, penile neoplasmsAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- May 13, 2024 – BUFFALO, NY- May 13, 2024 – Impact Journals publishes scholarly journals in the biomedical sciences, with a focus on all areas of cancer and aging research. Oncotarget is one of the most prominent journals published by Impact Journals.Impact Journals is proud to participate at the Society for Scholarly Publishing (SSP) 46th Annual Meeting, which convenes in Boston, Massachusetts, at the Westin Boston Seaport District from May 29–31, 2024. This year, the SSP Annual Meeting theme is “Inflection Point: Setting the Course for the Future of Scholarly Communication.”Visit booth #212 at the SSP 46th Annual Meeting 2024 to connect with members of the Oncotarget team.About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open-access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
The profound impact of the COVID-19 pandemic, caused by the SARS-CoV-2 virus, has been felt across various domains, including the realm of cancer research and treatment. As scientists delve deeper into the intricate mechanisms of this viral pathogen, intriguing revelations have emerged regarding its potential influence on cellular processes pivotal to cancer development and progression. In a new study, researchers Wafik S. El-Deiry and Shengliang Zhang from Brown University and Lifespan Health System shed light on the intricate interplay between the SARS-CoV-2 spike protein and the tumor suppressor p53, a key guardian of genomic integrity. On May 3, 2024, they published their new research paper in Oncotarget’s Volume 15, entitled, “Transfected SARS-CoV-2 spike DNA for mammalian cell expression inhibits p53 activation of p21(WAF1), TRAIL Death Receptor DR5 and MDM2 proteins in cancer cells and increases cancer cell viability after chemotherapy exposure.”In this study, researchers El-Deiry and Zhang uncovered a hitherto unknown facet of the SARS-CoV-2 spike protein’s impact on cancer cells. Their findings, meticulously detailed in their research paper, have ignited a newfound curiosity within the scientific community.Full blog - https://www.oncotarget.org/2024/05/09/sars-cov-2-spike-protein-disrupts-p53-tumor-suppressor-pathway/Paper DOI - https://doi.org/10.18632/oncotarget.28582Correspondence to - Wafik S. El-Deiry - wafik@brown.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28582Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, SARS-COV2 spike, p53, MDM2, chemotherapyAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- May 8, 2024 – A new research paper was published in Oncotarget's Volume 15 on May 7, 2024, entitled, “Deep learning-based whole-body PSMA PET/CT attenuation correction utilizing Pix-2-Pix GAN.”The sequential PET/CT studies oncology patients can undergo during their treatment follow-up course is limited by radiation dosage. In this new study, researchers Kevin C. Ma, Esther Mena, Liza Lindenberg, Nathan S. Lay, Phillip Eclarinal, Deborah E. Citrin, Peter A. Pinto, Bradford J. Wood, William L. Dahut, James L. Gulley, Ravi A. Madan, Peter L. Choyke, Ismail Baris Turkbey, and Stephanie A. Harmon from the National Institutes of Health’s National Cancer Institute proposed an artificial intelligence (AI) tool to produce attenuation-corrected PET (AC-PET) images from non-attenuation-corrected PET (NAC-PET) images to reduce need for low-dose CT scans.“AI-generated PET images has clinical potential for reducing the need for CT scans for attenuation correction while preserving quantitative markers and image quality in prostate cancer patients.”Methods: A deep learning algorithm based on 2D Pix-2-Pix generative adversarial network (GAN) architecture was developed from paired AC-PET and NAC-PET images. 18F-DCFPyL PSMA (prostate-specific membrane antigen) PET-CT studies from 302 prostate cancer patients, split into training, validation, and testing cohorts (n = 183, 60, 59, respectively). Models were trained with two normalization strategies: Standard Uptake Value (SUV)-based and SUV-Nyul-based. Scan-level performance was evaluated by normalized mean square error (NMSE), mean absolute error (MAE), structural similarity index (SSIM), and peak signal-to-noise ratio (PSNR). Lesion-level analysis was performed in regions-of-interest prospectively from nuclear medicine physicians. SUV metrics were evaluated using intraclass correlation coefficient (ICC), repeatability coefficient (RC), and linear mixed-effects modeling.Results: Median NMSE, MAE, SSIM, and PSNR were 13.26%, 3.59%, 0.891, and 26.82, respectively, in the independent test cohort. ICC for SUVmax and SUVmean were 0.88 and 0.89, which indicated a high correlation between original and AI-generated quantitative imaging markers. Lesion location, density (Hounsfield units), and lesion uptake were all shown to impact relative error in generated SUV metrics (all p < 0.05).“The Pix-2-Pix GAN model for generating AC-PET demonstrates SUV metrics that highly correlate with original images. AI-generated PET images show clinical potential for reducing the need for CT scans for attenuation correction while preserving quantitative markers and image quality.”DOI - https://doi.org/10.18632/oncotarget.28583Correspondence to - Stephanie A. Harmon - stephanie.harmon@nih.govSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28583Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- May 6, 2024 – A new research paper was published in Oncotarget's Volume 15 on May 3, 2024, entitled, “Transfected SARS-CoV-2 spike DNA for mammalian cell expression inhibits p53 activation of p21(WAF1), TRAIL Death Receptor DR5 and MDM2 proteins in cancer cells and increases cancer cell viability after chemotherapy exposure.”Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 infection has led to worsened outcomes for patients with cancer. SARS-CoV-2 spike protein mediates host cell infection and cell-cell fusion that causes stabilization of tumor suppressor p53 protein. In-silico analysis previously suggested that SARS-CoV-2 spike interacts with p53 directly but this putative interaction has not been demonstrated in cells. In this new study, researchers Shengliang Zhang and Wafik S. El-Deiry from Brown University and Lifespan Health System examined the interaction between SARS-CoV-2 spike, p53 and MDM2 (E3 ligase, which mediates p53 degradation) in cancer cells using an immunoprecipitation assay. “We observed that SARS-CoV-2 spike protein interrupts p53-MDM2 protein interaction but did not detect SARS-CoV-2 spike bound with p53 protein in the cancer cells.”The researchers further observed that SARS-CoV-2 spike suppresses p53 transcriptional activity in cancer cells including after nutlin exposure of wild-type p53-, spike-expressing tumor cells and inhibits chemotherapy-induced p53 gene activation of p21(WAF1), TRAIL Death Receptor DR5 and MDM2. The suppressive effect of SARS-CoV-2 spike on p53-dependent gene activation provides a potential molecular mechanism by which SARS-CoV-2 infection may impact tumorigenesis, tumor progression and chemotherapy sensitivity. In fact, cisplatin-treated tumor cells expressing spike were found to have increased cell viability as compared to control cells. Further observations on γ-H2AX expression in spike-expressing cells treated with cisplatin may indicate altered DNA damage sensing in the DNA damage response pathway. The preliminary observations reported here warrant further studies to unravel the impact of SARS-CoV-2 and its various encoded proteins including spike on pathways of tumorigenesis and response to cancer therapeutics. More efforts should be directed at studying the effects of the SARS-CoV-2 spike and other viral proteins on host DNA damage sensing, response and repair mechanisms. “A goal would be to understand the structural basis for maximal anti-viral immunity while minimizing suppression of host defenses including the p53 DNA damage response and tumor suppression pathway. Such directions are relevant and important including not only in the context of viral infection and mRNA vaccines in general but also for patients with cancer who may be receiving cytotoxic or other cancer treatments.”DOI - https://doi.org/10.18632/oncotarget.28582Correspondence to - Wafik S. El-Deiry - wafik@brown.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28582Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/MEDIA@IMPACTJOURNALS.COM
BUFFALO, NY- April 29, 2024 – Oncotarget is a contributing #sponsor at the 19th International p53 Workshop, organized by the International Center for Genetic Engineering and Biotechnology (ICGEB), which takes place from May 13–16, 2024, in Trieste, Italy.“Groundbreaking research and cutting-edge advancements in the field of the most studied human gene and most frequently mutated gene in cancer, will take center stage at the 19th International p53 Workshop.” – ICGEB.orgAmong the 24 invited speakers at the 19th International p53 Workshop, 18 speakers have published new research on p53 in Oncotarget. These distinguished speakers who have published with Oncotarget include Dr. Andrei Gudkov — one of Oncotarget’s founding Editors-in-Chief. Dr. Gudkov will be speaking in the session on “p53 Inflammation and Immunity” and moderating the session on “Targeting p53 in Human Disease.”“The event will gather leading scientists, clinicians, and researchers from around the world providing a unique opportunity to delve into the latest discoveries and innovations related to TP53 biology and explore the intricate role of TP53 in cancer and its potential for transformative impact in oncology.” – ICGEB.orgAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- April 16, 2024 – A new #researchpaper was #published in Oncotarget's Volume 15 on April 12, 2024, entitled, “Novel therapeutic bispecific antibodies for B-cell lymphoma targeting IgM and other antigens on the B-cell surface.”The B-cell receptor regulates B-cell proliferation and apoptosis. Aberrations in BCR signaling are associated with the development and progression of B-cell malignancies, such as mantle cell lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia, many of which express the IgM type of BCR on their cellular surface. Therefore, IgM is an attractive target for therapeutic antibodies against B-cell malignancies. However, soluble IgM competitively binds to anti-IgM antibodies in the serum, and these antibodies show insufficient cytotoxic activity. Thus, antibody therapy targeting IgM is hindered by the presence of soluble IgM in the blood. In this new study, researchers Takahiro Ohashi, Sayuri Terada, Shinsuke Hiramoto, Yuko Nagata, Hirokazu Suzuki, Hitoshi Miyashita, Tetsuo Sasaki, Yasukatsu Tsukada, and Keiko Fukushima from ZENOAQ (Zenyaku Kogyo Co., Ltd.) used a bispecific antibody to address this problem. “In this study, we aimed to produce IgM-dependent bispecific antibodies targeting IgM and the other B-cell antigens such as CD20, CD32b (FcγRIIB), CD79b, and human leukocyte antigen (HLA)-DR using the Cys1m technology [10, 43–45]. Additionally, the correct IgG-like bispecific antibody structures were confirmed and their efficacies in the presence of soluble IgM were analyzed.”The researchers generated bispecific antibodies bound to IgM and other B-cell antigens such as CD20 and HLA-DR using their own bispecific antibody-producing technology, Cys1m. These bispecific antibodies directly inhibited cell proliferation via cell-cycle arrest and apoptosis in vitro, although large amounts of soluble IgM were present. Additionally, a bispecific antibody bound to IgM and HLA-DR (BTA106) depleted B-cells in cynomolgus monkeys. “These data suggest that anti-IgM/B-cell surface antigen-binding specific antibodies are promising therapeutic agents for B-cell malignancies. Moreover, the bispecific antibody modality can potentially overcome problems caused by soluble antigens.”DOI - https://doi.org/10.18632/oncotarget.28578Correspondence to - Keiko Fukushima - keiko_fukushima@mail.zenyaku.co.jpSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28578Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, bispecific antibody, Cys1m, IgM, lymphoma, cynomolgus monkeyAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
Acute myeloid leukemia (AML) is a cancer characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. ABT199, also known as venetoclax, is a targeted therapy that inhibits the BCL-2 protein, which is often overexpressed in AML cells and contributes to their survival. By blocking this protein, venetoclax can trigger apoptosis, or programmed cell death, in cancer cells. Thiotepa, a DNA alkylating agent, has been used in conditioning regimens for hematopoietic stem cell transplantation (HSCT) but its combination with ABT199/venetoclax has not been thoroughly explored, until now.In a new study, researchers Benigno C. Valdez, Bin Yuan, David Murray, Jeremy L. Ramdial, Uday Popat, Yago Nieto, and Borje S. Andersson from The University of Texas MD Anderson Cancer Center and the University of Alberta investigated a promising new approach to AML therapy by combining multiple drugs to enhance cytotoxic effects on AML cells. On March 14, 2024, their new research paper was published in Oncotarget’s Volume 15, entitled, “ABT199/venetoclax synergism with thiotepa enhances the cytotoxicity of fludarabine, cladribine and busulfan in AML cells.”Full blog - https://www.oncotarget.org/2024/04/11/synergistic-effects-of-drug-combinations-targeting-aml-cells/Paper DOI - https://doi.org/10.18632/oncotarget.28563Correspondence to - Benigno C. Valdez - mbalasik@yahoo.comSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28563Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, acute myeloid leukemia, aml, pre-transplant regimens, venetoclax, thiotepa, busulfanAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- April 10, 2024 – A new #researchpaper was #published in Oncotarget's Volume 15 on April 8, 2024, entitled, “Exploring the role of GHRH antagonist MIA-602 in overcoming Doxorubicin-resistance in acute myeloid leukemia.”Acute myeloid leukemia (AML) is characterized by the rapid proliferation of mutagenic hematopoietic progenitors in the bone marrow. Conventional therapies include chemotherapy and bone marrow stem cell transplantation; however, they are often associated with poor prognosis. Notably, growth hormone-releasing hormone (GHRH) receptor antagonist MIA-602 has been shown to impede the growth of various human cancer cell lines, including AML. In this new study, researchers Simonetta I. Gaumond, Rama Abdin, Joel Costoya, Andrew V. Schally, and Joaquin J. Jimenez from the University of Miami, Florida Atlantic University and Veterans Affairs Medical Center, Miami examined the impact of MIA-602 as monotherapy and in combination with Doxorubicin on three Doxorubicin-resistant AML cell lines, KG-1A, U-937, and K-562. “Given the role of GHRH in multiple cancer types, it is possible that GHRH antagonists may offer an alternative treatment approach for AML as well as drug-resistant AML, which may circumvent the side effects associated with standard chemotherapy.”The in vitro results revealed a significant reduction in cell viability for all treated wild-type cells. Doxorubicin-resistant clones were similarly susceptible to MIA-602 as the wild-type counterpart. Their in vivo experiment of xenografted nude mice with Doxorubicin-resistant K-562 revealed a reduction in tumor volume with MIA-602 treatment compared to control. “Our study demonstrates that these three AML cell lines, and their Doxorubicin-resistant clones, are susceptible to GHRH antagonist MIA-602.”DOI - https://doi.org/10.18632/oncotarget.28579Correspondence to - Simonetta I. Gaumond - sxg1204@miami.eduSubscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, leukemia, AML, resistance, growth hormone-releasing hormone, MIA-602About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
Cancer therapy has come a long way from its one-size-fits-all beginning to the awakening era of personalized medicine. This change has been largely driven by the discovery of biomarkers. Biomarkers can help refine patient selection for specific therapies. A blend of causal and correlative approaches is needed to elucidate the full potential of biomarkers in cancer research. This fusion of methodologies allows for a comprehensive exploration of biomarker efficacy, leading to more accurate predictions of drug response.In a new paper, researchers Alberto Moscona-Nissan, Karl J. Habashy, Victor A. Arrieta, Adam M. Sonabend, and Crismita Dmello from the Universidad Panamericana School of Medicine, Northwestern University and Universidad Nacional Autónoma de México discuss causal and correlative approaches to identify potential biomarkers for predicting response to paclitaxel — a commonly used chemotherapeutic agent. On February 8, 2024, their research perspective was published in Oncotarget’s Volume 15, entitled, “Combining causal and correlative approaches to discover biomarkers of response to paclitaxel.”“[…] studying the combination of non-overlapping biomarkers’ expression, in addition to clinical and sociodemographic data could generate predictive models for paclitaxel susceptibility.”Full blog - https://www.oncotarget.org/2024/03/28/identifying-biomarkers-for-predicting-paclitaxel-response/Paper DOI - https://doi.org/10.18632/oncotarget.28549Correspondence to - Crismita Dmello - crismita.dmello@northwestern.edu, and Adam M. Sonabend - adam.sonabend@northwestern.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28549Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, glioblastoma, predictive biomarker, CRISPR screen, paclitaxelAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- March 27, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on March 19, 2024, entitled, “Durvalumab and tremelimumab before surgery in patients with hormone receptor positive, HER2-negative stage II–III breast cancer.”In this new study, researchers Haven R. Garber, Sreyashi Basu, Sonali Jindal, Zhong He, Khoi Chu, Akshara Singareeka Raghavendra, Clinton Yam, Lumarie Santiago, Beatriz E. Adrada, Padmanee Sharma, Elizabeth A. Mittendorf, and Jennifer K. Litton from the University of Texas MD Anderson Cancer Center, Brigham and Women’s Hospital, Dana-Farber Brigham Cancer Center, and Harvard Medical School conducted a clinical trial to assess the feasibility of enrolling patients with Stage II or III hormone receptor positive (HR+)/HER2-negative breast cancer to pre-operative dual PD-L1/CTLA-4 checkpoint inhibition administered prior to neoadjuvant chemotherapy (NACT). “This feasibility study was conducted to begin testing the hypothesis that dual checkpoint blockade would increase TIL and enhance the response to subsequent NACT in patients with stage II or III HR+/HER2-negative breast cancer.”Eight eligible patients were treated with upfront durvalumab and tremelimumab for two cycles. Patients then received NACT prior to breast surgery. Seven patients had baseline and interval breast ultrasounds after combination immunotherapy and the responses were mixed: 3/7 patients experienced a ≥30% decrease in tumor volume, 3/7 a ≥30% increase, and 1 patient had stable disease. At the time of breast surgery, 1/8 patients had a pathologic complete response (pCR).The trial was stopped early after 3 of 8 patients experienced immunotherapy-related toxicity or suspected disease progression that prompted discontinuation or a delay in the administration of NACT. Two patients experienced grade 3 immune-related adverse events (1 with colitis, 1 with endocrinopathy). Analysis of the tumor microenvironment after combination immunotherapy did not show a significant change in immune cell subsets from baseline.“There was limited benefit for dual checkpoint blockade administered prior to NACT in our study of 8 patients with HR+/HER2-negative breast cancer.”DOI - https://doi.org/10.18632/oncotarget.28567Correspondence to - Haven R. Garber - hrgarber@mdanderson.orgSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28567Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, breast cancer, ER positive, immunotherapy, neoadjuvant chemotherapy, tumor microenvironmentAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- March 25, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on March 14, 2024, entitled, “ABT199/venetoclax synergism with thiotepa enhances the cytotoxicity of fludarabine, cladribine and busulfan in AML cells.”ABT199/venetoclax, an inhibitor of the pro-survival BCL-2 protein, has improved AML treatment. Its efficacy in hematopoietic stem cell transplantation (HSCT), when combined with other chemotherapeutic drugs, has not been thoroughly investigated. In this new study, researchers Benigno C. Valdez, Bin Yuan, David Murray, Jeremy L. Ramdial, Uday Popat, Yago Nieto, and Borje S. Andersson from The University of Texas MD Anderson Cancer Center and the University of Alberta demonstrate the synergistic cytotoxicity of ABT199/venetoclax with the DNA alkylator thiotepa (Thio) in AML cells. “The results may provide relevant information for the design of clinical trials using these drugs to circumvent recognized drug-resistance mechanisms when used as part of pre-transplant conditioning regimens for AML patients undergoing allogenic HSCT.”Cleavage of Caspase 3, PARP1 and HSP90, as well as increased Annexin V positivity, suggest potent activation of apoptosis by this two-drug combination; increased levels of γ-H2AX, P-CHK1 (S317), P-CHK2 (S19) and P-SMC1 (S957) indicate an enhanced DNA damage response. Likewise, the increased level of P-SAPK/JNK (T183/Y185) and decreased P-PI3Kp85 (Y458) suggest enhanced activation of stress signaling pathways. These molecular readouts were synergistically enhanced when ABT199/venetoclax and Thio were combined with fludarabine, cladribine and busulfan. The five-drug combination decreased the levels of BCL-2, BCL-xL and MCL-1, suggesting its potential clinical relevance in overcoming ABT199/venetoclax resistance. Moreover, this combination is active against P53-negative and FLT3-ITD-positive cell lines. Enhanced activation of apoptosis was observed in leukemia patient-derived cell samples exposed to the five-drug combination, suggesting a clinical relevance. “The results provide a rationale for clinical trials using these two- and five-drug combinations as part of a conditioning regimen for AML patients undergoing HSCT.”DOI - https://doi.org/10.18632/oncotarget.28563Correspondence to - Benigno C. Valdez - mbalasik@yahoo.comSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28563Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, acute myeloid leukemia, aml, pre-transplant regimens, venetoclax, thiotepa, busulfanAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- March 20, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on March 14, 2024, entitled, “Analytical validation of NeXT Personal®, an ultra-sensitive personalized circulating tumor DNA assay.”In this new study, researchers Josette Northcott, Gabor Bartha, Jason Harris, Conan Li, Fabio C.P. Navarro, Rachel Marty Pyke, Manqing Hong, Qi Zhang, Shuyuan Ma, Tina X. Chen, Janet Lai, Nitin Udar, Juan-Sebastian Saldivar, Erin Ayash, Joshua Anderson, Jiang Li, Tiange Cui, Tu Le, Ruthie Chow, Randy Jerel Velasco, Chris Mallo, Rose Santiago, Robert C. Bruce, Laurie J. Goodman, Yi Chen, Dan Norton, Richard O. Chen, and John M. Lyle from Personalis, Inc. describe the analytical validation of NeXT Personal®, an ultra-sensitive, tumor-informed circulating tumor DNA (ctDNA) assay for detecting residual disease, monitoring therapy response, and detecting recurrence in patients diagnosed with solid tumor cancers. “NeXT Personal uses whole genome sequencing of tumor and matched normal samples combined with advanced analytics to accurately identify up to ~1,800 somatic variants specific to the patient’s tumor.” A personalized panel is created, targeting these variants and then used to sequence cell-free DNA extracted from patient plasma samples for ultra-sensitive detection of ctDNA. The NeXT Personal analytical validation is based on panels designed from tumor and matched normal samples from two cell lines, and from 123 patients across nine cancer types. Analytical measurements demonstrated a detection threshold of 1.67 parts per million (PPM) with a limit of detection at 95% (LOD95) of 3.45 PPM. NeXT Personal showed linearity over a range of 0.8 to 300,000 PPM (Pearson correlation coefficient = 0.9998). Precision varied from a coefficient of variation of 12.8% to 3.6% over a range of 25 to 25,000 PPM. The assay targets 99.9% specificity, with this validation study measuring 100% specificity and in silico methods giving a confidence interval of 99.92 to 100%.“In summary, this study demonstrates NeXT Personal as an ultra-sensitive, highly quantitative and robust ctDNA assay that can be used to detect residual disease, monitor treatment response, and detect recurrence in patients.”DOI - https://doi.org/10.18632/oncotarget.28565Correspondence to - John M. Lyle - john.lyle@personalis.com Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28565Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, circulating tumor DNA, whole genome sequencing, molecular residual disease, tumor-informed assay, analytical validationOncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- March 19, 2024 – A new #research perspective was #published by Mikhail V. Blagosklonny M.D., Ph.D., from Roswell Park Comprehensive Cancer Center in Oncotarget's Volume 15 on March 15, 2024, entitled, “From osimertinib to preemptive combinations.”“Here, I suggest that while first-line osimertinib extends median progression-free survival (PFS) in EGFR-mutant lung cancer compared to first-generation TKIs, it reduces individual PFS in 15–20% of patients compared to first-generation TKIs. Since detecting a single resistant cell before treatment is usually impossible, osimertinib must be used in all patients as a first-line treatment, raising median PFS overall but harming some. The simplest remedy is a preemptive combination (PC) of osimertinib and gefitinib. A comprehensive PC (osimertinib, afatinib/gefitinib, and capmatinib) could dramatically increase PFS for 80% of patients compared to osimertinib alone, without harming anyone. This article also explores PCs for MET-driven lung cancer.”DOI - https://doi.org/10.18632/oncotarget.28569Correspondence to - Mikhail V. Blagosklonny - Blagosklonny@oncotarget.com, Blagosklonny@rapalogs.comSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28569Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, lung cancer, NSCLC, EGFR, resistance, afatinib, gefitinib, capmatinibAbout Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- March 18, 2024 – A new #researchpaper was #published in Oncotarget's Volume 15 on March 14, 2024, entitled, “G-quadruplex landscape and its regulation revealed by a new antibody capture method.”In this new study, researchers Subhamoy Datta, Manthan Patel, Chakkarai Sathyaseelan, Chandrama Ghosh, Akanksha Mudgal, Divyesh Patel, Thenmalarchelvi Rathinavelan, and Umashankar Singh from the Indian Institute of Technology Gandhinagar, Indian Institute of Technology Hyderabad, Queen Mary University of London, Bar-Ilan University, Medical University of Lublin, and the University of Helsinki discuss a secondary structure of DNA that has attracted wide interest, G-quadruplexes or G4s.“Our understanding of DNA G-quadruplexes (G4s) from in vitro studies has been complemented by genome-wide G4 landscapes from cultured cells.”Conventionally, the formation of G4s is accepted to depend on G-repeats such that they form tetrads. However, genome-wide G4s characterized through high-throughput sequencing suggest that these structures form at a large number of regions with no such canonical G4-forming signatures. Many G4-binding proteins have been described with no evidence for any protein that binds to and stabilizes G4s. “It remains unknown what fraction of G4s formed in human cells are protein-bound.” The G4-chromatin immunoprecipitation (G4-ChIP) method hitherto employed to describe G4 landscapes preferentially reports G4s that get crosslinked to proteins in their proximity. The current understanding of the G4 landscape is biased against representation of G4s which escape crosslinking as they are not stabilized by protein-binding and presumably transient. The researchers reported a protocol that captures G4s from the cells efficiently without any bias as well as eliminates the detection of G4s formed artifactually on crosslinked sheared chromatin post-fixation. They discovered that G4s form sparingly at SINEs (short interspersed nuclear elements). An application of this method shows that depletion of a repeat-binding protein CGGBP1 enhances net G4 capture at CGGBP1-dependent CTCF-binding sites and regions of sharp interstrand G/C-skew transitions. “The AbC G4-ChIP presents a powerful technique to decipher the cellular G4 landscape and its regulation and it has the potential to be adapted for discovering any DNA secondary structures genome-wide against which reliable antibodies are available.”DOI - https://doi.org/10.18632/oncotarget.28564Correspondence to - Umashankar Singh - usingh@iitgn.ac.inSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28564Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, DNA G-quadruplexes, G4-ChIP, CGGBP1, CTCF, G/C-skewOncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMEDIA@IMPACTJOURNALS.COM
The relentless search for effective cancer therapies has led to numerous breakthroughs in drug discovery and development. Advancements have emerged in recent years through the promising avenue of combination therapy, where two or more drugs are used synergistically to enhance their collective therapeutic effect. This strategy has shown significant potential in overcoming drug resistance, reducing side effects, and improving patient survival rates.In a new study, researchers Thomas M. Cardillo, Maria B. Zalath, Roberto Arrojo, Robert M. Sharkey, Serengulam V. Govindan, Chien-Hsing Chang, and David M. Goldenberg from Gilead Sciences and the Center for Molecular Medicine and Immunology demonstrated the significant antitumor effects of Sacituzumab govitecan, an anti-Trop-2-SN-38 antibody-drug conjugate, in combination with platinum-based chemotherapy. On February 22, 2024, their research paper was published in Oncotarget, entitled, “Sacituzumab govitecan plus platinum-based chemotherapy mediates significant antitumor effects in triple-negative breast, urinary bladder, and small-cell lung carcinomas.”Full blog - https://www.oncotarget.org/2024/03/14/antitumor-effects-of-sacituzumab-govitecan-plus-platinum-based-chemotherapy/Paper DOI - https://doi.org/10.18632/oncotarget.28559Correspondence to - Thomas M. Cardillo - Thomas.Cardillo1@Gilead.comSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28559Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, sacituzumab govitecan, Trop-2, SN-38, carboplatin, cisplatinAbout OncotargetOncotarget is an open-access, peer-reviewed journal that has published primarily oncology-focused research papers since 2010. These papers are available to readers (at no cost and free of subscription barriers) in a continuous publishing format at Oncotarget.com. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- March 11, 2024 – Impact Journals publishes #scholarly journals in the #biomedical sciences with a focus on all areas of cancer and aging research. Oncotarget is one of the most prominent journals published by Impact Journals. Impact Journals will be participating as an exhibitor at the American Association for Cancer Research (AACR) Annual Meeting 2024 from April 5-10 at the San Diego Convention Center in San Diego, California. This year, the AACR meeting theme is “Inspiring Science • Fueling Progress • Revolutionizing Care.”Visit booth number 4159 at the AACR Annual Meeting 2024 to connect with members of the Oncotarget team.About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open-access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us on social media at:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- March 6, 2024 – A new #researchpaper was #published in Oncotarget's Volume 15 on March 5, 2024, entitled, “GZ17-6.02 interacts with proteasome inhibitors to kill multiple myeloma cells.”In this new study, researchers Laurence Booth, Jane L. Roberts, Cameron West, and Paul Dent from Virginia Commonwealth University and Genzada Pharmaceuticals investigated GZ17-6.02, a synthetically manufactured compound containing isovanillin, harmine and curcumin, in multiple myeloma cells. GZ17-6.02 has undergone phase I evaluation in patients with solid tumors (NCT03775525) with a recommended phase 2 dose (RP2D) of 375 mg PO BID. GZ17-6.02 was more efficacious as a single agent at killing multiple myeloma cells than had previously been observed in solid tumor cell types. “GZ17-6.02 interacted with proteasome inhibitors in a greater than additive fashion to kill myeloma cells and alone it killed inhibitor-resistant cells to a similar extent.”The drug combination of GZ17-6.02 and bortezomib activated ATM, the AMPK and PERK and inactivated ULK1, mTORC1, eIF2α, NFκB and the Hippo pathway. The combination increased ATG13 S318 phosphorylation and the expression of Beclin1, ATG5, BAK and BIM, and reduced the levels of BCL-XL and MCL1. GZ17-6.02 interacted with bortezomib to enhance autophagosome formation and autophagic flux, and knock down of ATM, AMPKα, ULK1, Beclin1 or ATG5 significantly reduced both autophagy and tumor cell killing. Knock down of BAK and BIM significantly reduced tumor cell killing. The expression of HDACs1/2/3 was significantly reduced beyond that previously observed in solid tumor cells and required autophagy. This was associated with increased acetylation and methylation of histone H3. Combined knock down of HDACs1/2/3 caused activation of ATM and the AMPK and caused inactivation of ULK1, mTORC1, NFκB and the Hippo pathway. HDAC knock down also enhanced ATG13 phosphorylation, increased BAK levels and reduced those of BCL-XL. “Collectively, our present studies support performing additional in vivo studies with multiple myeloma cells.”DOI - https://doi.org/10.18632/oncotarget.28558Correspondence to - Paul Dent - paul.dent@vcuhealth.orgSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28558Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, autophagy, ER stress, GZ17-6.02, bortezomib, proteasome inhibitorAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- March 4, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on February 22, 2024, entitled, “Sacituzumab govitecan plus platinum-based chemotherapy mediates significant antitumor effects in triple-negative breast, urinary bladder, and small-cell lung carcinomas.”Sacituzumab govitecan (SG) is an antibody-drug conjugate composed of an anti-Trop-2-directed antibody conjugated with the topoisomerase I inhibitory drug, SN-38, via a proprietary hydrolysable linker. SG has received United States Food and Drug Administration (FDA) approval to treat metastatic triple-negative breast cancer (TNBC), unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, and accelerated approval for metastatic urothelial cancer (mUC).In this new study, researchers Thomas M. Cardillo, Maria B. Zalath, Roberto Arrojo, Robert M. Sharkey, Serengulam V. Govindan, Chien-Hsing Chang, and David M. Goldenberg from Gilead Sciences and the Center for Molecular Medicine and Immunology investigated the utility of combining SG with platinum-based chemotherapeutics in TNBC, urinary bladder carcinoma (UBC), and small-cell lung carcinoma (SCLC). “Given recent FDA approval of SG in mTNBC and accelerated approval in mUC [metastatic urothelial cancer], as well as its demonstrated clinical activity in SCLC [11], we investigated the possibility of expanding use of SG through combinations with currently utilized chemotherapeutics for these disease indications.”SG plus carboplatin or cisplatin produced additive growth-inhibitory effects in vitro that trended towards synergy. Immunoblot analysis of cell lysates suggests perturbation of the cell-cycle and a shift towards pro-apoptotic signaling evidenced by an increased Bax to Bcl-2 ratio and down-regulation of two anti-apoptotic proteins, Mcl-1 and survivin. Significant antitumor effects were observed with SG plus carboplatin in mice bearing TNBC or SCLC tumors compared to all controls (P < 0.0062 and P < 0.0017, respectively) and with SG plus cisplatin in UBC and SCLC tumor-bearing animals (P < 0.0362 and P < 0.0001, respectively). These combinations were well tolerated by the animals. “Combining SG with platinum-based chemotherapeutics demonstrates the benefit in these indications and warrants further clinical investigation.”DOI - https://doi.org/10.18632/oncotarget.28559Correspondence to - Thomas M. Cardillo - Thomas.Cardillo1@Gilead.comSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28559Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, sacituzumab govitecan, Trop-2, SN-38, carboplatin, cisplatinAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- February 28, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on February 22, 2024, entitled, “Prevalence and spectrum of germline BRCA1 and BRCA2 in a cohort of ovarian cancer patients from the Salento peninsula (Southern Italy): a matter of preventive health.”In this new exploratory and descriptive study, researchers Elisabetta De Matteis, Maria Rosaria Tumolo, Paolo Tarantino, Mariangela Ciccarese, Tiziana Grassi, Francesco Bagordo, Maria Rita De Giorgio, Emanuele Rizzo, and Graziana Ronzino from Vito Fazzi Hospital, University of Salento, Strategic Regional Agency for Health and Social of Puglia, and University of Bari Aldo Moro aimed to characterize the deleterious BRCA1 and BRCA2 variants evaluated by genetic testing in a group of Ovarian cancer patients living in the Salento peninsula (Southern Italy).From June 2014 to July 2023, patients with histologically confirmed high-grade serous carcinoma, fallopian tube, or primary peritoneal cancer who were referred to Lecce Familial Cancer Clinic were considered. BRCA-mutation genetic testing was performed on these patients. Socio-demographic data and cancer epidemiology were assessed, and Next Generation Sequencing and Sanger DNA sequencing were performed.The median age at the diagnosis of 332 ovarian cancer patients collected was 57 years. The pedigree analyses showed that 28.6% had familial cases and 39.7% had sporadic cases. Of the 319 patients submitted to genetic testing, 29.8% were carriers of BRCA1/2 mutation, 75.8% at BRCA1 and 24.2% at BRCA2 gene. Of the 21 BRCA1 mutations, the variant c.5266dupC was the most frequent alteration (28.4%). With respect to BRCA2, 13 mutations were found and the variant c.9676delT was the most frequently recorded (6.3%).“This study reveals that the prevalence of germline mutations in the BRCA1 and BRCA2 genes was higher than reported by other studies. A broader understanding of the prevalence and role of BRCA mutations in development, response to treatment, and prognosis represents an exciting and developing area of ovarian cancer treatment and prevention.”DOI - https://doi.org/10.18632/oncotarget.28561Correspondence to - Maria Rosaria Tumolo - mariarosaria.tumolo@unisalento.itSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28561Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, ovarian cancer, BRCA1, BRCA2, mutationAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- February 26, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on February 8, 2024, entitled, “GZ17-6.02 interacts with bexarotene to kill mycosis fungoides cells.”In this new study, researchers Michael R. Booth, Laurence Booth, Jane L. Roberts, Cameron West, and Paul Dent from Virginia Commonwealth University and Genzada Pharmaceuticals investigated the therapeutic agent GZ17-6.02, composed of curcumin, harmine and isovanillin.“Combined with our curcumin findings, we believe that isovanillin can complex with curcumin and harmine to create an entity with unique biology when compared to the three individual agents.”GZ17-6.02 has undergone phase I evaluation in patients with solid tumors (NCT03775525) with an RP2D of 375 mg PO BID. The biology of GZ17-6.02 in malignant T cells and in particular those derived from mycosis fungoides (MF) patients, has not previously been studied. The researchers found that GZ17-6.02 alone and in combination with standard-of-care agents was effective in killing MF cells. “All three components are necessary for optimal killing of MF cells.” GZ17-6.02 activated ATM, the AMPK, NFκB and PERK and inactivated ERK1/2, AKT, ULK1, mTORC1, eIF2α, and reduced the expression of BCL-XL and MCL1. GZ17-6.02 increased ATG13 S318 phosphorylation and the expression of Beclin1, ATG5, BAK and BIM. GZ17-6.02 in a dose-dependent fashion enhanced autophagosome formation and autophagic flux, and tumor cell killing. Signaling by ATM and AMPK were both required for efficient killing but not for the dose-response effect whereas ER stress (eIF2α) and macroautophagy (Beclin1, ATG5) were required for both efficient killing and the dose-response. Knock down of the death receptor CD95 reduced killing by ~20% and interacted with autophagy inhibition to further reduce killing, collectively, by ~70%. Inhibition of autophagy and knock down of death-mediators downstream of the mitochondrion, AIF and caspase 3, almost abolished tumor cell killing. Hence in MF cells, the team wrote that GZ17-6.02 is a multi-factorial killer, utilizing ER stress, macroautophagy, death receptor signaling and directly causing mitochondrial dysfunction.” “We discovered that GZ17-6.02 containing harmine, isovanillin and curcumin caused more tumor cell killing than any of the agents individually or in pairs, and that it could interact in an additive fashion with standard of care MF drugs such as bexarotene and vorinostat to cause additional tumor cell death.”DOI - https://doi.org/10.18632/oncotarget.28557Correspondence to - Paul Dent - paul.dent@vcuhealth.orgSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28557Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, autophagy, ER stress, GZ17-6.02, bexarotene, vorinostatAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
Betel quid chewing, a traditional custom widely practiced in South Asia, Southeast Asia, the Asia-Pacific region, and East Africa for centuries, involves the consumption of raw areca nut mixed with slaked lime and wrapped in a betel leaf. This habit is particularly popular in certain regions, including Northeast India, where the areca nut is raw, wet, and consumed unprocessed. The act of chewing and swallowing this mixture leads to the release of alkaloids, polyphenols, and tannins. However, the consumption of raw areca nut betel quid has been strongly associated with the development of oral, esophageal, and gastric cancers, and has adverse consequences on oral health. Several studies have shown a significant relationship between periodontitis and betel quid chewing habits in many countries, including India.In this context, esophageal cancer is a devastating disease that affects millions of people around the world. Recent research has shed light on the role of the Mad2 gene in the development and progression of esophageal cancer, a disease strongly associated with the consumption of raw areca nut betel quid. In a new study, researchers Chongtham Sovachandra Singh, Nabamita Boruah, Atanu Banerjee, Sillarine Kurkalang, Pooja Swargiary, Hughbert Dakhar, and Anupam Chatterjee from The Assam Royal Global University, University of Pennsylvania, LN Mithila University, University of Chicago Medicine, Nazareth Hospital, Laitumkhrah, and North-Eastern Hill University provide valuable insights into the molecular mechanisms underlying Mad2 gene deregulation in esophageal cancer. On February 5, 2024, their new research paper was published in Oncotarget’s Volume 15, entitled, “Differential expression of Mad2 gene is consequential to the patterns of histone H3 post-translational modifications in its promoter region in human esophageal cancer samples.”Full blog - https://www.oncotarget.org/2024/02/22/raw-areca-nut-betel-quid-consumption-and-esophageal-cancer/Paper DOI - https://doi.org/10.18632/oncotarget.28554Correspondence to - Anupam Chatterjee - achatterjee@rgu.ac, chatterjeeanupam@hotmail.comSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28554Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, Mad2 gene, histone methylation, histone acetylation, Rb-phosphorylation; esophageal cancerAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- February 21, 2024 – A new research #perspective was #published in Oncotarget's Volume 15 on February 8, 2024, entitled, “Combining causal and correlative approaches to discover biomarkers of response to paclitaxel.”As discussed in this new paper, researchers Alberto Moscona-Nissan, Karl J. Habashy, Victor A. Arrieta, Adam M. Sonabend, and Crismita Dmello from Universidad Panamericana School of Medicine, Northwestern University and Universidad Nacional Autónoma de México recently discovered a putative paclitaxel response predictive biomarker for glioblastoma and breast cancer using the whole genome CRISPR knockout screen. The biomarker candidate was validated in two independent breast cancer patient cohorts that received taxane treatment. “To further evaluate the potential application of this biomarker in the clinic for patients with glioblastoma, a prospective validation in cohorts of patients with glioblastoma is essential and will be performed as part of our ongoing phase II clinical trial (NCT04528680).”The validation of novel biomarkers of susceptibility to therapy is critical to elucidate the efficacy signal of therapeutic agents. This is especially important in the context of glioblastoma, where therapeutic benefit is variable and unpredictable, leading to negative trials, yet the outcome of subset of patients has outperformed expectations.“Precision and personalized medicine can lead to a transition from a stochastic treatment response into predictable scenarios. Further identification of predictive biomarkers, validation, and study of combinations as predictive models is critical to generate a greater impact that can be translated to the bedside of patients.”DOI - https://doi.org/10.18632/oncotarget.28549Correspondence to - Crismita Dmello - crismita.dmello@northwestern.edu, and Adam M. Sonabend - adam.sonabend@northwestern.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28549Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, glioblastoma, predictive biomarker, CRISPR screen, paclitaxelAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- February 19, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on February 5, 2024, entitled, “Neurotrophic-tyrosine receptor kinase gene fusion in papillary thyroid cancer: A clinicogenomic biobank and record linkage study from Finland.”Selective tropomyosin receptor kinase (TRK) inhibitors are approved targeted therapies for patients with solid tumors harboring a neurotrophic tyrosine receptor kinase (NTRK) gene fusion. Country-specific estimates of NTRK gene fusion frequency, and knowledge on the characteristics of affected patients, are limited.In this new study, researchers Wei Zhang, Arndt A. Schmitz, Roosa E. Kallionpää, Merja Perälä, Niina Pitkänen, Mikko Tukiainen, Erika Alanne, Korinna Jöhrens, Renate Schulze-Rath, Bahman Farahmand, and Jihong Zong from Bayer HealthCare Pharmaceuticals Inc., University of Turku, Turku University Hospital, Technical University Dresden, and Western Finland Cancer Centre identified patients with histologically-confirmed papillary thyroid cancer (PTC) from Finland’s Auria Biobank. “The study objectives were to determine the frequency of NTRK gene fusion in patients with PTC in Finland, and to describe co-occurring genetic alternations, clinical characteristics, disease progression, and treatment pathways in NTRK gene fusion positive patients.”TRK protein expression was determined by pan-TRK immunohistochemistry. Immuno-stained tumor samples were scored by a certified pathologist. Gene fusions and other co-occurring gene alterations were identified by next generation sequencing. Patient characteristics and vital status were determined from linked hospital electronic health records (EHRs). Patients were followed from 1 year before PTC diagnosis until death. 6/389 (1.5%) PTC patients had an NTRK gene fusion (all NTRK3); mean age 43.8 years (and none had comorbidities) at PTC diagnosis. Gene fusion partners were EML4 (n = 3), ETV6 (n = 2), and RBPMS (n = 1). Of 3/6 patients with complete EHRs, all received radioactive iodine ablation only and were alive at end of follow-up (median observation, 9.12 years). “In conclusion, NTRK gene fusion is infrequent in patients with PTC. Linkage of biobank samples to EHRs is feasible in describing the characteristics and outcomes of patients with PTC and potentially other cancer types.”DOI - https://doi.org/10.18632/oncotarget.28555Correspondence to - Jihong Zong - jihong.zong@bayer.comSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28555Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, NTRK gene fusion, papillary thyroid cancer, clinicogenomic, epidemiology, biobankAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
Crossref is a non-profit organization that logs and updates citations for scientific publications. Each month, Crossref identifies a list of the most popular Oncotarget papers based on the number of times a DOI is successfully resolved. Below are Crossref’s Top 10 Oncotarget DOIs published in 2023.10: Everolimus downregulates STAT3/HIF-1α/VEGF pathway to inhibit angiogenesis and lymphangiogenesis in TP53 mutant head and neck squamous cell carcinoma (HNSCC)DOI: https://doi.org/10.18632/oncotarget.28355 Authors: Md Maksudul Alam, Janmaris Marin Fermin, Mark Knackstedt, Mackenzie J. Noonan, Taylor Powell, Landon Goodreau, Emily K. Daniel, Xiaohua Rong, Tara Moore-Medlin, Alok R. Khandelwal, and Cherie-Ann O. Nathan9: Novel inflammation-combined prognostic index to predict survival outcomes in patients with gastric cancerDOI: https://doi.org/10.18632/oncotarget.28353 Authors: Noriyuki Hirahara, Takeshi Matsubara, Shunsuke Kaji, Hikota Hayashi, Yohei Sasaki, Koki Kawakami, Ryoji Hyakudomi, Tetsu Yamamoto, and Yoshitsugu Tajima8: Crosstalk between triple negative breast cancer and microenvironmentDOI: https://doi.org/10.18632/oncotarget.28397 Authors: Karly Smrekar, Artem Belyakov and Kideok Jin7: Systemic AL amyloidosis: current approach and future directionDOI: https://doi.org/10.18632/oncotarget.28415 Authors: Maroun Bou Zerdan, Lewis Nasr, Farhan Khalid, Sabine Allam, Youssef Bouferraa, Saba Batool, Muhammad Tayyeb, Shubham Adroja, Mahinbanu Mammadii, Faiz Anwer, Shahzad Raza, and Chakra P. Chaulagain6: Deciphering the mechanisms of action of progesterone in breast cancerDOI: https://doi.org/10.18632/oncotarget.28455 Authors: Gaurav Chakravorty, Suhail Ahmad, Mukul S. Godbole, Sudeep Gupta, Rajendra A. Badwe, and Amit Dutt5: Targeting cellular respiration as a therapeutic strategy in glioblastomaDOI: https://doi.org/10.18632/oncotarget.28424 Authors: Enyuan Shang, Trang Thi Thu Nguyen, Mike-Andrew Westhoff, Georg Karpel-Massler, and Markus D. Siegelin4: Selective protection of normal cells from chemotherapy, while killing drug-resistant cancer cellsDOI: https://doi.org/10.18632/oncotarget.28382 Author: Mikhail V. Blagosklonny, M.D., Ph.D. 3: The immunoregulatory protein CD200 as a potentially lucrative yet elusive target for cancer therapyDOI: https://doi.org/10.18632/oncotarget.28354 Authors: Anqi Shao and David M. Owens2: Genomic landscape of metastatic breast cancer (MBC) patients with methylthioadenosine phosphorylase (MTAP) lossDOI: https://doi.org/10.18632/oncotarget.28376 Authors: Maroun Bou Zerdan, Prashanth Ashok Kumar, Elio Haroun, Nimisha Srivastava, Jeffrey Ross, and Abirami Sivapiragasam1: Using cancer proteomics data to identify gene candidates for therapeutic targetingDOI: https://doi.org/10.18632/oncotarget.28420 Authors: Diana Monsivais, Sydney E. Parks, Darshan S. Chandrashekar, Sooryanarayana Varambally, and Chad J. CreightonOncotarget is an open-access, peer-reviewed journal that has published primarily oncology-focused research papers since 2010. These papers are available to readers (at no cost and free of subscription barriers) in a continuous publishing format at Oncotarget.com. Oncotarget is indexed/archived on MEDLINE / PMC / PubMed.For media inquiries, please contact media@impactjournals.com.
BUFFALO, NY- February 14, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on February 5, 2024, entitled, “Genetic and therapeutic landscapes in cohort of pancreatic adenocarcinomas: next-generation sequencing and machine learning for full tumor exome analysis.”About 7% of all cancer deaths are caused by pancreatic cancer (PCa). PCa is known for its lowest survival rates among all oncological diseases and heterogenic molecular profile. Enormous amount of genetic changes, including somatic mutations, exceeds the limits of routine clinical genetic laboratory tests and further stagnates the development of personalized treatments. In this new study, researchers P.A. Shatalov, N.A. Falaleeva, E.A. Bykova, D.O. Korostin, V.A. Belova, A.A. Zabolotneva, A.P. Shinkarkina, A. Yu Gorbachev, M.B. Potievskiy, V.S. Surkova, Zh V. Khailova, N.A. Kulemin, Denis Baranovskii, A.A. Kostin, A.D. Kaprin, and P.V. Shegai from the Ministry of Health of the Russian Federation, Pirogov Russian National Research Medical University, Federal Medical-Biological Agency, Moscow, and the Peoples Friendship University of Russia (RUDN University) aimed to build a mutational landscape of PCa in the Russian population based on full exome next-generation sequencing (NGS) of the limited group of patients. “Applying a machine learning model on full exome individual data, we received personalized recommendations for targeted treatment options for each clinical case and summarized them in the unique therapeutic landscape.”DOI - https://doi.org/10.18632/oncotarget.28512Correspondence to - Denis Baranovskii - doc.baranovsky@gmail.comSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28512Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, pancreatic cancer, tumor mutation burden, somatic mutations, artificial intelligence, machine learningAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- February 12, 2024 – A new research paper was published in Oncotarget's Volume 15 on February 5, 2024, entitled, “Differential expression of Mad2 gene is consequential to the patterns of histone H3 post-translational modifications in its promoter region in human esophageal cancer samples.”Raw areca nut (AN) consumption increases esophageal squamous cell carcinoma (ESCC) due to overexpression of securin (pituitary tumor transforming gene1), causing chromosomal instability. Mitotic arrest deficient protein 2 (Mad2), a crucial spindle assembly checkpoint protein, is at risk of aneuploidy and tumor development when overexpressed or underexpressed. In this new study, researchers Chongtham Sovachandra Singh, Nabamita Boruah, Atanu Banerjee, Sillarine Kurkalang, Pooja Swargiary, Hughbert Dakhar, and Anupam Chatterjee from The Assam Royal Global University, University of Pennsylvania, LN Mithila University, University of Chicago Medicine, Nazareth Hospital, Laitumkhrah, and North-Eastern Hill University evaluated Mad2 status in human ESCC with AN consumption habits, revealing unclear molecular mechanisms. Human ESCC samples (n = 99) were used for loss of heterozygosity analysis at 4q25-28, while 32 samples were used for expression analysis of Mad2, E2F1 genes, and Rb-phosphorylation. Blood samples were used for metaphase preparation. The Mad2 deregulation was assessed using chromatin immunoprecipitation-qPCR assay in the core promoter region, establishing its association with the pRb-E2F1 circuit for the first time. “The study revealed overexpression and underexpression of Mad2, premature anaphase, and chromosome missegregation in all the samples.” LOH pattern identified a deletion in D4S2975 in 40% of ESCC samples. The study reveals the deregulation of pRb-E2F1 circuit in all samples. 4q27 disruption could be a factor for Mad2 underexpression in AN-induced esophageal carcinogenesis, while overexpression may be due to the deregulation of the Rb-E2F1 circuit and consequently elevation of H3K4me3 and H3K9ac. “Mad2 expression levels with chromosomal abnormalities can be a clinical biomarker, but further research is needed to understand pRb’s role in Mad2 down-regulation.”DOI - https://doi.org/10.18632/oncotarget.28554Correspondence to - Anupam Chatterjee - achatterjee@rgu.ac, chatterjeeanupam@hotmail.comSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28554Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, Mad2 gene, histone methylation, histone acetylation, Rb-phosphorylation; esophageal cancerAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
Thyroid cancer is a complex disease with various subtypes and clinical presentations. While some cases can be successfully treated with standard therapy, others present challenges due to resistance to treatment and the development of aggressive forms of the disease. In a new research perspective, researchers Mark Lee and Luc GT Morris from New York Presbyterian Hospital and Memorial Sloan Kettering Cancer Center discuss the recent research that has shed light on the role of genetic alterations in mediating both resistance to BRAF inhibition and anaplastic transformation in thyroid cancer. On January 24, 2024, their paper was published in Oncotarget, entitled, “Genetic alterations in thyroid cancer mediating both resistance to BRAF inhibition and anaplastic transformation.”“An improved understanding of the molecular basis of thyroid cancer has led to the development of new targeted agents.”Full blog - https://www.oncotarget.org/2024/02/08/genetic-alterations-in-thyroid-cancer-resistance-to-brafi-and-anaplastic-transformation/DOI - https://doi.org/10.18632/oncotarget.28544Correspondence to - Luc GT Morris - morrisl@mskcc.orgSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28544Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, thyroid cancer, drug resistance, anaplastic transformation, BRAF inhibitors, PIK3CAAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957Paper DOI -
BUFFALO, NY- February 7, 2024 – A new #research perspective was #published in Oncotarget's Volume 15 on February 5, 2024, entitled, “Preclinical and clinical evaluation of the Janus Kinase inhibitor ruxolitinib in multiple myeloma.”In this new paper, researchers Ashley Del Dosso, Elizabeth Tadevosyan, and James R. Berenson from ONCOtherapeutics, Berenson Cancer Center, and Institute for Myeloma and Bone Cancer Research discussed multiple myeloma (MM) — the most common primary malignancy of the bone marrow. No established curative treatment is currently available for patients diagnosed with MM. In recent years, new and more effective drugs have become available for the treatment of this B-cell malignancy. These new drugs have often been evaluated together and in combination with older agents. However, even these novel combinations eventually become ineffective; and, thus, novel therapeutic approaches are necessary to help overcome resistance to these treatments. Recently, the Janus Kinase (JAK) family of tyrosine kinases, specifically JAK1 and JAK2, has been shown to have a role in the pathogenesis of MM. Preclinical studies have demonstrated a role for JAK signaling in direct and indirect growth of MM and downregulation of anti-tumor immune responses in these patients. Also, inhibition of JAK proteins enhances the anti-MM effects of other drugs used to treat MM. These findings have been confirmed in clinical studies which have further demonstrated the safety and efficacy of JAK inhibition as a means to overcome resistance to currently available anti-MM therapies. Additional studies will provide further support for this promising new therapeutic approach for treating patients with MM.“The following sections of this article will be focused on studies of RUX [Ruxolitinib] in the preclinical [21–24] and clinical settings [18–20] focused on the treatment of relapsed/refractory (RR) MM.”DOI - https://doi.org/10.18632/oncotarget.28547Correspondence to - James R. Berenson - jberenson@berensoncancercenter.comSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28547Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, multiple myeloma, ruxolitinib, JAK/STAT, cytokine, clinical trialAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- February 5, 2024 – A new #editorial paper was #published in Oncotarget's Volume 15 on January 24, 2024, entitled, “The fate of drug discovery in academia; dumping in the publication landfill?”In this new editorial, researchers Uzma Saqib, Isaac S. Demaree, Alexander G. Obukhov, Mirza S. Baig, Amiram Ariel, and Krishnan Hajela, from Devi Ahilya Vishwavidyalaya, Indore, discuss drug discovery—a tedious process that is time consuming in both divulging whether a molecule is efficacious and specific in hitting the target and also in confirming that the potential drug does not cause severe adverse effects. Many drug candidates fail crossing multiple checkpoints of this long journey; they lag in one or several aspects and never move beyond the research bench to contribute to public health. These setbacks make the process of drug discovery very time consuming, expensive, and tedious. “This viewpoint is focused on delineating how and why the multi-million [dollar] research efforts in the field of drug discovery often fail to reach its full potential.”There is no shortage of studies focusing on drug discovery. They are published on a daily basis describing the efforts encompassing conventional and/or modern drug discovery technology, including structure-based drug design (SBDD), virtual screening, high-throughput screening (HTS), Artificial Intelligence (AI), and cell-based screening approaches (Figure 1). However, many drug development strategies are rather fuzzy in their advancement. Thus, there is a large gap between drug “discovery” and “development.” This part could be attributed to the lack of synergy between Academia and Industry at multiple levels. A significant part of this failure results from the lack of streamlining of drug development process. “In the current perspective, we discussed why many therapeutic molecules never make it to clinical studies despite being proven efficacious pre-clinically. Additionally, we discussed the possible solutions to overcome this défaut of the drug development process.”DOI - https://doi.org/10.18632/oncotarget.28552Correspondence to - Krishnan Hajela - hajelak@gmail.comSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28552Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, drug discovery and development, clinical trials, academia-industry collaboration, translational research, drug databaseAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- January 31, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on January 24, 2024, entitled, “BCAS1 defines a heterogeneous cell population in diffuse gliomas.”Oligodendrocyte precursor markers have become of great interest to identify new diagnostic and therapeutic targets for diffuse gliomas, since state-of-the-art studies point towards immature oligodendrocytes as a possible source of gliomagenesis. Brain enriched myelin associated protein 1 (BCAS1) is a novel marker of immature oligodendrocytes and was proposed to contribute to tumorigenesis in non-central nervous system tumors. However, the role of BCAS1 in diffuse glioma is still underexplored. In this new study, researchers Raquel Morales-Gallel, María José Ulloa-Navas, Patricia García-Tárraga, Ricardo Prat-Acín, Gaspar Reynés, Pedro Pérez-Borredá, Luis Rubio, Vivian Capilla-González, Jaime Ferrer-Lozano, and José Manuel García-Verdugo from the University of Valencia-CIBERNED, Mayo Clinic, Hospital Universitari i Politècnic La Fe, University of Pablo de Olavide, and University of Seville-CSIC analyzed the expression of BCAS1 in different tumor samples from patients with diffuse gliomas (17 oligodendrogliomas; 8 astrocytomas; 60 glioblastomas) and uncovered the molecular and ultrastructural features of BCAS1+ cells by immunostaining and electron microscopy. “Our results show that BCAS1+ cells exhibit stellate or spherical morphology with similar ultrastructural features.”Stellate and spherical cells were detected as isolated cells in all studied gliomas. Nevertheless, only stellate cells were found to be proliferative and formed tightly packed nodules with a highly proliferative rate in oligodendrogliomas. Their findings provide a comprehensive characterization of the BCAS1+ cell population within diffuse gliomas. The observed proliferative capacity and distribution of BCAS1+ stellate cells, particularly in oligodendrogliomas, highlight BCAS1 as an interesting marker, warranting further investigation into its role in tumor malignancy.“In conclusion, this insight will shed light on the establishment of BCAS1 as a clinically relevant molecule, serving not only as a diagnostic or prognostic marker but also as a novel therapeutic target for the development of cutting-edge treatments.”DOI - https://doi.org/10.18632/oncotarget.28553Correspondence to - José Manuel García-Verdugo - j.manuel.garcia@uv.esSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28553Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, brain tumor, diffuse glioma, oligodendroglioma, glioblastoma, BCAS1About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- January 29, 2024 – A new #research perspective was #published in Oncotarget's Volume 15 on January 24, 2024, entitled, “Genetic alterations in thyroid cancer mediating both resistance to BRAF inhibition and anaplastic transformation.”In this new paper, researchers Mark Lee and Luc GT Morris from New York Presbyterian Hospital and Memorial Sloan Kettering Cancer Center discuss thyroid cancer. A subset of thyroid cancers present at advanced stage or with dedifferentiated histology and have limited response to standard therapy. Tumors harboring the BRAF V600E mutation may be treated with BRAF inhibitors; however, tumor response is often short-lived due to multiple compensatory resistance mechanisms. “One mode of resistance is the transition to an alternative cell state, which on rare occasions can correspond to tumor dedifferentiation.” DNA sequencing and RNA expression profiling show that thyroid tumors that dedifferentiate after BRAF inhibition are enriched in known genetic alterations that mediate resistance to BRAF blockade, and may also drive tumor dedifferentiation, including mutations in the PI3K/AKT/MTOR (PIK3CA, MTOR), MAP/ERK (MET, NF2, NRAS, RASA1), SWI/SNF chromatin remodeling complex (ARID2, PBRM1), and JAK/STAT pathways (JAK1). Given these findings, recent investigations have evaluated the efficacy of dual-target therapies; however, continued lack of long-term tumor control illustrates the complex and multifactorial nature of these compensatory mechanisms. Transition to an immune-suppressed state is another correlate of BRAF inhibitor resistance and tumor dedifferentiation, suggesting a possible role for concurrent targeted therapy with immunotherapy. “Investigations into combined targeted and immunotherapy are ongoing, but early results with checkpoint inhibitors, viral therapies, and CAR T-cells suggest enhanced anti-tumor immune activity with these combinations.”DOI - https://doi.org/10.18632/oncotarget.28544Correspondence to - Luc GT Morris - morrisl@mskcc.orgSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28544Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, thyroid cancer, drug resistance, anaplastic transformation, BRAF inhibitors, PIK3CAAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
Glioblastoma is a type of brain cancer that is very aggressive and difficult to treat. The current standard treatment involves surgery, radiation therapy, and chemotherapy with a drug called temozolomide (TMZ). However, many glioblastoma cells can resist the DNA-damaging effects of TMZ and radiation by activating a mechanism called the DNA damage response (DDR). This mechanism, while beneficial in normal cells, is detrimental to cancer therapy because it allows cancer cells to repair damage and continue to grow and divide. There is a need to counteract this mechanism in glioblastoma cancer cells.In a new study, researchers Mathew Lozinski, Nikola A. Bowden, Moira C. Graves, Michael Fay, Bryan W. Day, Brett W. Stringer, and Paul A. Tooney from University of Newcastle, Hunter Medical Research Institute, GenesisCare, QIMR Berghofer Medical Research Institute, and Griffith University found that a drug called gartisertib may overcome this resistance by inhibiting a key protein involved in the DDR, called ataxia-telangiectasia and Rad3-Related protein (ATR). On January 16, 2024, the researchers published their new research paper in Oncotarget’s Volume 15, entitled, “ATR inhibition using gartisertib enhances cell death and synergises with temozolomide and radiation in patient-derived glioblastoma cell lines.”Full blog - https://www.oncotarget.org/2024/01/25/new-drug-may-boost-effectiveness-of-glioblastoma-treatment/Paper DOI - https://doi.org/10.18632/oncotarget.28551Correspondence to - Paul A. Tooney - paul.tooney@newcastle.edu.auSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28551Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, glioblastoma, DNA damage response, ataxia-telangiectasia and rad3-related protein, radiation therapy, temozolomideAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- January 24, 2024 – A new #case report was #published in Oncotarget's Volume 15 on January 16, 2024, entitled, “Lazarus effect in a patient initially empirically treated with osimertinib for EGFR L858R mutant non-small cell lung cancer with leptomeningeal disease: a case report.”Osimertinib has been shown to be effective for patients with non-small cell lung cancer (NSCLC) with activating EGFR mutations. These patients are also at risk for leptomeningeal disease (LMD). LMD is characterized by central nervous system metastases with spread to the cerebrospinal fluid or leptomeninges. In patients with NSCLC with EGFR activating mutations, there is an increased occurrence of LMD, which occurs in 9% of patients.In this new report, researchers Shreya Bhatia, Manuel G. Cortez, Spencer Lessans, and Wade T. Iams from Vanderbilt-Ingram Cancer Center present a patient of East Asian descent whose initial presentation included severe, progressive leptomeningeal carcinomatosis and a small lung mass, with limited tissue available for molecular testing. She responded to empiric, urgent initiation of osimertinib, repeat tissue sampling revealed an EGFR L858R mutation, and she has experienced durable disease improvement for 18 months on osimertinib monotherapy.“Our case demonstrates the nuances of decision-making in starting osimertinib in urgent clinical settings. Given our patient’s progressively worsening functional status and spread of disease to her CNS upon presentation, there was a need to begin treatment imminently. Time constraints, financial constraints, and lack of sufficient tissue for analysis ultimately led to the empiric use of osimertinib. Through the urgent initiation of appropriate anti-cancer therapy, she experienced both a life saving improvement in functional status and improvement in her LUL primary tumor one month into treatment.”DOI - https://doi.org/10.18632/oncotarget.28550Correspondence to - Wade T. Iams - wade.t.iams@vumc.orgSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28550Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, EGFR mutation, leptomeningeal disease, non-small cell lung cancer, osimertinibAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh?si=&nd=1&dlsi=c12c9dbac1be421dMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- January 22, 2024 – On January 3, 2024, Mikhail V. Blagosklonny M.D., Ph.D., from Roswell Park Comprehensive Cancer Center #published a new brief #report in Oncoscience (Volume 11), entitled, “My battle with cancer. Part 1.”“In January 2023, diagnosed with numerous metastases of lung cancer in my brain, I felt that I must accomplish a mission. If everything happens for a reason, my cancer, in particular, I must find out how metastatic cancer can be treated with curative intent. This is my mission now, and the reason I was ever born. In January 2023, I understood the meaning of life, of my life. I was born to write this article. In this article, I argue that monotherapy with targeted drugs, even when used in sequence, cannot cure metastatic cancer. However, preemptive combinations of targeted drugs may, in theory, cure incurable cancer. Also, I share insights on various topics, including rapamycin, an anti-aging drug that can delay but not prevent cancer, through my personal journey.”DOI - https://doi.org/10.18632/oncoscience.593Corresponding author - Mikhail V. Blagosklonny - Blagosklonny@oncotarget.com, Blagosklonny@rapalogs.comSign up for free Altmetric alerts about this article -https://oncoscience.altmetric.com/details/email_updates?id=10.18632%2Foncoscience.593Subscribe for free publication alerts from Oncoscience - https://www.oncoscience.us/subscribe/Keywords - cancer, lung cancer, brain metastases, capmatinib, resistance, METAbout OncoscienceOncoscience is a traditional, peer-reviewed, bio-medical oncology research journal with FREE publication for authors and open-access for readers.To learn more about Oncoscience, please visit https://www.oncoscience.us/ and connect with us:Facebook - https://www.facebook.com/OncoscienceX - https://twitter.com/OncoscienceJrnlInstagram - https://www.instagram.com/oncosciencejrnl/YouTube - https://www.youtube.com/@OncoscienceJournalLinkedIn - https://www.linkedin.com/company/oncoscience/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- January 22, 2024 – A new #research perspective was #published in Oncotarget's Volume 15 on January 16, 2024, entitled, “Bone marrow adipocytes provide early sign for progression from MGUS to multiple myeloma.”Multiple Myeloma (MM) is the second most common hematological malignancy and is characterized by clonal expansion of malignant plasma cells in the bone marrow. In spite of recent advances in the field of MM, the disease has remained incurable. MM is preceded by a premalignant state known as monoclonal gammopathy of undetermined significance (MGUS), with a risk of progression to MM of 1% per year. Establishing a scalable approach that refines the identification of MGUS patients at high risk of progression to MM can transform the clinical management of the disease, improve the patient’s quality of life, and will have significant socioeconomic implications. In this new perspective, researchers Bilal M. El-Masri, Benedeta Leka, Fatima Mustapha, Michael Tveden Gundesen, Maja Hinge, Thomas Lund, Thomas L. Andersen, Marta Diaz-delCastillo, and Abbas Jafari from the Danish Spatial Imaging Consortium, University of Southern Denmark, University of Copenhagen, University of Aarhus, Odense University Hospital, and Lillebaelt Hospital provide evidence that changes in the bone marrow adipose tissue (BMAT) provide an early sign for progression from MGUS to MM. “We employed AI-assisted histological analysis of unstained bone marrow biopsies from MGUS subjects with or without progression to MM within 10 years (n = 24, n = 17 respectively).” Although the BMAT fraction was not different between the two groups, bone marrow adipocyte (BMAd) density was decreased in MGUS patients who developed MM, compared to non-progressing MGUS patients. Importantly, the distribution profile for BMAd size and roundness was significantly different between the two groups, indicating a shift toward increased BMAd size and roundness in MGUS patients who developed MM. These early changes in the BMAT could serve as valuable early indicators for the transition from MGUS to MM, potentially enabling timely interventions and personalized treatment strategies. “[...] the AI-based approach for histological characterization of unstained bone marrow biopsies is cost-effective and fast, rendering its clinical implementation feasible.”DOI - https://doi.org/10.18632/oncotarget.28548Correspondence to - Abbas Jafari - ajafari@sund.ku.dk, Marta Diaz-delCastillo - marta@forens.au.dk, and Thomas L. Andersen - thomas.levin.andersen@rsyd.dkSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28548Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, multiple myeloma, MGUS, bone marrow adipocyteAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:Facebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVhMedia ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- January 17, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on January 16, 2024, entitled, “ATR inhibition using gartisertib enhances cell death and synergises with temozolomide and radiation in patient-derived glioblastoma cell lines.”Glioblastoma cells can restrict the DNA-damaging effects of temozolomide (TMZ) and radiation therapy (RT) using the DNA damage response (DDR) mechanism which activates cell cycle arrest and DNA repair pathways. Ataxia-telangiectasia and Rad3-Related protein (ATR) plays a pivotal role in the recognition of DNA damage induced by chemotherapy and radiation causing downstream DDR activation. In this new study, researchers Mathew Lozinski, Nikola A. Bowden, Moira C. Graves, Michael Fay, Bryan W. Day, Brett W. Stringer, and Paul A. Tooney from University of Newcastle, Hunter Medical Research Institute, GenesisCare, QIMR Berghofer Medical Research Institute, and Griffith University investigated the activity of the ATR inhibitor gartisertib alone, and in combination with TMZ and/or RT, in multiple patient-derived glioblastoma cell lines. “Using a panel of 12 patient-derived glioblastoma cell lines, we investigated the chemo- and radio-sensitizing effect of gartisertib, a potent and selective inhibitor of ATR [26] that was explored in a phase 1 clinical trial for patients with advanced solid tumors (NCT02278250).”The team showed that gartisertib alone potently reduced the cell viability of glioblastoma cell lines, where sensitivity was associated with the frequency of DDR mutations and higher expression of the G2 cell cycle pathway. ATR inhibition significantly enhanced cell death in combination with TMZ and RT and was shown to have higher synergy than TMZ+RT treatment. MGMT promoter unmethylated and TMZ+RT resistant glioblastoma cells were also more sensitive to gartisertib. Analysis of gene expression from gartisertib treated glioblastoma cells identified the upregulation of innate immune-related pathways. “Overall, this study identifies ATR inhibition as a strategy to enhance the DNA-damaging ability of glioblastoma standard treatment, while providing preliminary evidence that ATR inhibition induces an innate immune gene signature that warrants further investigation.”DOI - https://doi.org/10.18632/oncotarget.28551Correspondence to - Paul A. Tooney - paul.tooney@newcastle.edu.auSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28551Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, glioblastoma, DNA damage response, ataxia-telangiectasia and rad3-related protein, radiation therapy, temozolomideAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- January 16, 2024 – A new #editorial paper was #published in Oncotarget's Volume 14 on December 1, 2023, entitled, “Reductive carboxylation of glutamine as a potential target in acute myeloid leukemia.”In this new editorial, researchers Alessia Roma, Lawrence D. Goodridge and Paul A. Spagnuolo from the University of Guelph discuss acute myeloid leukemia (AML) — an aggressive cancer of the blood and bone marrow defined by poor patient outcomes and sub-optimal therapeutics. Recent advancements in our understanding of AML biology bring optimism to improving patient outcomes for this devastating disease. For example, the discovery and validation of metabolic vulnerabilities that are distinct to AML open new strategies for novel drug development. In fact, since 2017, a third of newly approved AML therapeutics have targeted metabolic abnormalities. Thus, further identification and elucidation of metabolic vulnerabilities in AML could lead to novel therapies aimed at improving patient outcomes. “One approach is to weaken tumor cell survival mechanisms. In this regard, exploring reductive carboxylation as a possible drug target could provide new avenues for optimizing existing treatments aimed at improving AML patient outcomes.”DOI - https://doi.org/10.18632/oncotarget.28474Correspondence to - Paul A. Spagnuolo - paul.spagnuolo@uoguelph.caSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28474Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, acute myeloid leukemia, aml, reductive carboxylation, metabolism, mitochondria, complex IAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Mitochondrial biogenesis, the process of increasing the size and number of mitochondria within cells, plays a crucial role in cancer metastasis. Metastasizing cells exhibit a unique metabolism that differs from the well-known Warburg effect observed in primary tumors. While primary tumors primarily rely on glycolysis for energy production, metastatic cells rely on oxidative phosphorylation and ATP generation for short-term energy needs. However, over longer time frames, mitochondrial biogenesis becomes a prominent feature in the success of metastasis.In a new study, researchers Gulimirerouzi Fnu and Georg F. Weber from the University of Cincinnati’s James L. Winkle College of Pharmacy investigate the connection between short-term oxidative metabolism and long-term mitochondrial biogenesis in cancer metastasis. They hypothesized that Osteopontin splice variants, specifically Osteopontin-c, stimulate an increase in mitochondrial size through the activation of specific signaling mechanisms. On December 1, 2023, their new research paper was published in Oncotarget, entitled, “Osteopontin induces mitochondrial biogenesis in deadherent cancer cells.”Full blog - https://www.oncotarget.org/2024/01/11/how-osteopontin-stimulates-mitochondrial-mass-and-cancer-metastasis/Paper DOI - https://doi.org/10.18632/oncotarget.28540Correspondence to - Georg F. Weber - georg.weber@uc.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28540Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, metastasis, metabolism, anchorage independence, mitochondrial mass, peroxideAbout OncotargetOncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- January 10, 2024 – A new #editorial paper was #published in Oncotarget's Volume 14 on December 22, 2023, entitled, “One more step toward treatment of PARP inhibitor-resistant ovarian cancers.”Over 80% of ovarian cancer cases experience recurrence, resulting in roughly 12,000 annual deaths in the United States. While targeted therapies like poly (ADPribose) polymerase inhibitors (PARPis) have received FDA approval for both initial and recurrent treatments, extending median progression-free survival for individuals with homologous recombination repair (HRR) deficiency, the emergence of PARPi resistance remains a common challenge among patients. Consequently, addressing resistance to PARPi treatment in ovarian cancer has become a pressing therapeutic dilemma, necessitating innovative strategies. In this editorial, researchers Upasana Ray, Prabhu Thirusangu and Viji Shridhar from Mayo Clinic School of Medicine and Science responded to this unmet need with their current study, which unveiled promising findings related to the Pixatimod (PG545) drug, a sulfated small molecule compound. Engineered with a core structure mimicking heparan sulfate, this compound targets heparanase and heparin binding growth factor (HB-GF) signaling. “Our present study has revealed a previously unknown effect of PG545 in ovarian cancer cells, inducing DNA damage. The investigation unveiled that PG545 induces both single- and double-strand breaks in DNA while also promoting the autophagic degradation of RAD51, a critical DNA repair protein, thereby impeding the homologous recombination repair (HRR) pathway in cancer cells.”DOI - https://doi.org/10.18632/oncotarget.28545Correspondence to - Viji Shridhar - Shridhar.Vijayalakshmi@mayo.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28545Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, ovarian cancer, PARP inhibitors, PG545, DNA damage, cell deathAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- January 8, 2024 – A new #review paper was #published in Oncotarget's Volume 14 on December 22, 2023, entitled, “Transformation-associated recombination (TAR) cloning and its applications for gene function; genome architecture and evolution; biotechnology and biomedicine.”Transformation-associated recombination (TAR) cloning represents a unique tool to selectively and efficiently recover a given chromosomal segment up to several hundred kb in length from complex genomes (such as animals and plants) and simple genomes (such as bacteria and viruses). The technique exploits a high level of homologous recombination in the yeast Sacharomyces cerevisiae. “TAR cloning has become a valuable procedure for the selective and efficient isolation and manipulation of large DNA molecules. [...] The ability to isolate individual gene alleles will help to clarify whether a particular allele is associated with predisposition to different diseases, including cancer.”In this new review, researchers Natalay Kouprina and Vladimir Larionov from the National Cancer Institute's Developmental Therapeutics Branch summarized multiple applications of the pioneering TAR cloning technique, developed previously for complex genomes, for functional, evolutionary, and structural studies, and extended the modified TAR versions to isolate biosynthetic gene clusters (BGCs) from microbes, which are the major source of pharmacological agents and industrial compounds, and to engineer synthetic viruses with novel properties to design a new generation of vaccines. TAR cloning was adapted as a reliable method for the assembly of synthetic microbe genomes for fundamental research. “In this review, we also discuss how the TAR cloning in combination with HAC (human artificial chromosome)- and CRISPR-based technologies may contribute to the future.”DOI - https://doi.org/10.18632/oncotarget.28546Correspondence to - Natalay Kouprina - kouprinn@mail.nih.govSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28546Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, transformation-associated recombination, TAR, microbes, biomedicine, biotechnologyAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- January 3, 2024 – A new #editorial paper was #published in Oncotarget's Volume 14 on December 20, 2023, entitled, “Therapeutically harnessing cancer stem cell-derived exosomes.”In this editorial, researcher Yong Teng from Emory University discusses cancer stem cell-derived exosomes. Cancer stem cells (CSCs), a small population of cancer cells capable of self-renewal, are thought to serve as a central hub for tumor initiation, growth, metastasis, and recurrence. The potential for using CSCs in the diagnosis and treatment of cancer is gaining recognition. Exosomes are formed when multivesicular endosomes or multivesicular bodies fuse with the outer membrane of the cell, releasing various components such as DNA, RNA, lipids, metabolites, and cytosolic and cell surface proteins. “Over the past decade, our understanding of the characteristics and function of cancer-associated exosomes has expanded rapidly.”As the major messengers, exosomes present in the tumor microenvironment (TME) play a critical role in maintaining the delicate balance between CSCs and non-CSCs. Given the importance of CSCs, it is reasonable to believe that CSC-derived exosomes (CSC-Exos) are essential for communication between CSCs and other cells in the TME. Accumulating evidence has demonstrated that CSC-Exos contribute significantly to almost all fundamental aspects of cancer, including maintaining a continuous cycle of self-renewal within the TME, exerting control over neighboring or distant cells, enabling cancer cells to evade immune surveillance, and promoting immune tolerance. “A deeper understanding of the characteristics and functions of CSC-Exos has the potential to lay the foundation for the development of novel clinical tools for diagnosis and prognosis, as well as therapies aimed at preventing tumor progression and recurrence.”DOI - https://doi.org/10.18632/oncotarget.28542Correspondence to - Yong Teng - yong.teng@emory.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28542Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, cancer stem cells, exosomes, the tumor microenvironment, therapeutic target, anticancer strategyAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
In the realm of cancer research, the potential of melatonin as an anti-cancer agent has garnered significant attention. Over the past 50 years, numerous studies have been conducted to investigate the effects of melatonin on tumor growth and development in mice. These studies have provided valuable insights into the complex relationship between melatonin and carcinogenesis.In a new research perspective, researchers Vladimir N. Anisimov and Alexey G. Golubev from N.N. Petrov National Medical Research Center of Oncology wrote about the history of studies of melatonin effects on cancer in mice. Their paper was published in Oncotarget on December 12, 2023, entitled, “Melatonin and carcinogenesis in mice: the 50th anniversary of relationships.”Full blog - https://www.oncotarget.org/2023/12/28/melatonin-in-cancer-therapy-in-vivo-studies/Paper DOI - https://doi.org/10.18632/oncotarget.28537Correspondence to - Vladimir N. Anisimov - aging@mail.ruSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28537Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, melatonin, miceAbout OncotargetOncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- December 27, 2023 – A new #research paper was #published in Oncotarget's Volume 14 on December 20, 2023, entitled, “The pharmacodynamic and mechanistic foundation for the antineoplastic effects of GFH009, a potent and highly selective CDK9 inhibitor for the treatment of hematologic malignancies.” To evade cell cycle controls, malignant cells rely upon rapid expression of select proteins to mitigate pro-apoptotic signals resulting from damage caused by both cancer treatments and unchecked over-proliferation. Cyclin-dependent kinase 9 (CDK9)-dependent signaling induces transcription of downstream oncogenes promoting tumor growth, especially in hyperproliferative ‘oncogene-addicted’ cancers, such as human hematological malignancies (HHMs). In this new study, researchers Fusheng Zhou, Lili Tang, Siyuan Le, Mei Ge, Dragan Cicic, Fubo Xie, Jinmin Ren, Jiong Lan, and Qiang Lu from GenFleet Therapeutics Inc. and Sellas Life Sciences Group aimed to summarize current knowledge underlying the mechanism of action (MOA) of GFH009 and explain its robust anti-cancer activity. “Understanding GFH009’s MOA allows for a more optimal clinical development path, given the potential for meaningful benefits in patients with hematological malignancies.” GFH009, a potent, highly selective CDK9 small molecule inhibitor, demonstrated antiproliferative activity in assorted HHM-derived cell lines, inducing apoptosis at IC50 values below 0.2 μM in 7/10 lines tested. GFH009 inhibited tumor growth at all doses compared to controls and induced apoptosis in a dose-dependent manner. Twice-weekly injections of GFH009 maleate at 10 mg/kg significantly prolonged the survival of MV-4-11 xenograft-bearing rodents, while their body weight remained stable. There was marked reduction of MCL-1 and c-MYC protein expression post-drug exposure both in vitro and in vivo. Through rapid ‘on-off’ CDK9 inhibition, GFH009 exerts a proapoptotic effect on HHM preclinical models triggered by dynamic deprivation of crucial cell survival signals. “Our results mechanistically establish CDK9 as a targetable vulnerability in assorted HHMs and, along with the previously shown superior class kinome selectivity of GFH009 vs other CDK9 inhibitors, strongly support the rationale for currently ongoing clinical studies with this agent in acute myeloid leukemia and other HHMs.”DOI - https://doi.org/10.18632/oncotarget.28543Correspondence to - Jiong Lan - jlan@genfleet.comSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28543Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, GFH009, CDK9, leukemia, cell cycleAbout OncotargetOncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- December 20, 2023 – A new #review paper was #published in Oncotarget's Volume 14 on December 12, 2023, entitled, “Current perspectives on the management of refractory or relapsed classic hodgkin lymphoma in Brazil: Balancing efficacy, safety, and tolerability.”Classic Hodgkin lymphoma (CHL), which accounts for 90–95% of all cases of Hodgkin lymphoma, is the most frequent cancer in adolescents and the most frequent lymphoma in adolescents and young adults. Despite progressive improvements over past decades and the general sensitivity of CHL to frontline chemotherapy, approximately 10–15% of patients have refractory disease that either does not respond to such therapy or progresses after an initial partial response. In patients with refractory or relapsed disease, standard treatment until recently consisted mainly of salvage chemotherapy, in many cases followed by high-dose chemotherapy and autologous stem-cell transplantation. However, improved understanding of the pathobiology of CHL, coupled with the introduction of novel agents, has markedly changed the treatment landscape in the past decade. Although refractory or relapsed CHL continues to be challenging, the therapeutic landscape is undergoing profound changes brought about by novel agents, particularly brentuximab vedotin and immunotherapy. In this new review, researchers Flávia Dias Xavier, Danielle Leão Cordeiro de Farias, Abrahão Elias Hallack Neto, Glaciano Nogueira Ribeiro, Marco Aurelio Salvino de Araujo, Thiago Xavier Carneiro, and Otavio Cesar Carvalho Guimarães Baiocchi from Hospital Universitário de Brasília-Universidade de Brasília/Ebserh, Hospital DF Star, Hospital A Beneficência Portuguesa de São Paulo, Universidade Federal de Juiz de Fora, Clínica Hematológica/Grupo Oncoclinicas, Universidade Federal da Bahia, Instituto D'Or de Pesquisa e Ensino, Universidade Estadual do Pará, Universidade Federal de São Paulo, and Hospital Alemão Oswaldo Cruz discuss the most salient treatment options for adult patients with refractory or relapsed CHL, with a special focus on the Brazilian healthcare setting, which is constrained by inherent characteristics of this system. “In the attempt to balance efficacy, safety and tolerability, practicing physicians must rely on clinical trials and on results from real-world studies, and use their own point of view and experience, as well as patient characteristics and previous therapy, to make treatment decisions for refractory or relapsed CHL.”DOI - https://doi.org/10.18632/oncotarget.28541Correspondence to - Flávia Dias Xavier - flavia.xavier@unb.brSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28541Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, brentuximab vedotin, drug therapy, hodgkin lymphoma, nivolumab, pembrolizumabAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- December 18, 2023 – A new research #perspective was #published in Oncotarget's Volume 14 on December 12, 2023, entitled, “Melatonin and carcinogenesis in mice: the 50th anniversary of relationships.”Fifty years ago, in 1973, Vladimir N. Anisimov and coauthors demonstrated for the first time an inhibitory effect of the pineal gland hormone melatonin on cancer in vivo, namely on transplantable mammary tumors in mice. Subsequently, it was shown in a number of studies that melatonin administration with drinking water at night inhibits chemically induced mammary carcinogenesis in mice and rats.On the contrary, maintaining female mice and rats under round-the-clock lighting conditions, which suppresses the nighttime production of melatonin, stimulates spontaneous and chemical carcinogen-induced mammary tumor development.As of today, the query “cancer AND melatonin AND mice” in Pubmed returns about 550 entries. In this new research perspective, researchers Vladimir N. Anisimov and Alexey G. Golubev from N.N. Petrov National Medical Research Center of Oncology outline the history of studies of melatonin effects on cancer in mice, with the main lesson being that the systemic in vivo effects of melatonin on animals may overwhelm the in vitro effects found using tissue explants or cell cultures. “In particular, the timing of melatonin administration is of crucial importance for using the drug, which is freely available over [the] counter and thus needs no licensing for its applications in oncology.”DOI - https://doi.org/10.18632/oncotarget.28537Correspondence to - Vladimir N. Anisimov - aging@mail.ruSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28537Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, melatonin, miceAbout OncotargetOncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Colorectal cancer is the third most diagnosed cancer and the second leading cause of cancer-related deaths worldwide. It often starts in the colon or rectum with small, noncancerous clumps of cells called polyps, which can develop into cancer over time. Risk factors for colorectal cancer include age, family history, inflammatory bowel diseases, diet, smoking, and physical activity.The development and progression of colorectal cancer are driven by the aberrant activation of multiple signaling pathways, such as EGFR (epidermal growth factor receptor), RAS-RAF, and PTEN-PI3K. Among these pathways, the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathways are particularly important, as they are frequently mutated in colorectal cancer. Therapeutic targeting of these pathways has shown promise in suppressing tumor growth. However, cancer cells often develop resistance to targeted therapies, leading to treatment failure and disease progression.In a new study, researchers Astha Lamichhane, Gary D. Luker, Seema Agarwal, and Hossein Tavana from The University of Akron, University of Michigan and Georgetown University aimed to elucidate the role of cancer stemness in the resistance of colorectal cancer cells to targeted therapies. Their research paper was published in Oncotarget on October 4, 2023, entitled, “Inhibiting BRAF/EGFR/MEK suppresses cancer stemness and drug resistance of primary colorectal cancer cells.”Full blog - https://www.oncotarget.org/2023/12/14/triple-combination-treatment-overcomes-colorectal-cancer-resistance/Paper DOI - https://doi.org/10.18632/oncotarget.28517Correspondence to - Hossein Tavana - tavana@uakron.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28517Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, drug resistance, cancer stem cells, patient-derived tumor model, colorectal cancer, combination treatmentAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Dr. Georg F. Weber, from the University of Cincinnati Academic Health Center, James L. Winkle College of Pharmacy, describes a research paper he co-authored that was published by Oncotarget in Volume 14, entitled, “Osteopontin induces mitochondrial biogenesis in deadherent cancer cells.”DOI - https://doi.org/10.18632/oncotarget.28540Correspondence to - Georg F. Weber - georg.weber@uc.eduVideo interview - https://www.youtube.com/watch?v=ICGBwMKrq-ETranscript - https://www.oncotarget.net/2023/12/14/behind-the-study-osteopontin-induces-mitochondrial-biogenesis-in-deadherent-cancer-cells/Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28540Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, metastasis, metabolism, anchorage independence, mitochondrial mass, peroxideAbout OncotargetOncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- December 13, 2023 – A new #editorial paper was #published in Oncotarget's Volume 14 on December 1, 2023, entitled, “Therapeutic potentials and challenges of cytostatic persister cancer cells.”Cancer cells that remain viable despite treatment constitute a persister condition that is implicated in residual diseases and a source from which resistant clones and relapses can emerge. Unlike resistant cells that are capable of cycling under therapy, persister cancer cells stay viable but assume a quiescent or non-proliferating state that is reversible upon treatment discontinuation. A source of persisters that has been under extensive study is drug-tolerant persisters, a small cancer cell population that can withstand the selection pressure of cytotoxic treatment and have been attributed to failure in achieving complete response. It is well-recognized that many targeted therapeutic agents possess cytostatic effects that suppress growth without directly inducing cell death. While representing favorable responses, treatment-mediated cytostatic conditions require continual maintenance and intrinsically confer an obligate persister population throughout therapy. However, few efforts have focused on understanding the properties of such cytostatic persisters and exploring their therapeutic potentials.In their new editorial, researchers Paul Y. Kim and Cheuk T. Leung from the University of Minnesota Medical School discuss recent studies from their group exploring the cellular controls in persister cancer cells under treatment-mediated cytostatic conditions and devised strategies for targeting to reduce cancer recurrence. Findings shed light on the cellular controls in cytostatic persisters and highlighted that treatment-mediated cytostatic condition before resistance emerges is a viable targeting venue to reduce cancer recurrence.“The distinct vulnerabilities of cytostatic and drug-tolerant persisters imply that administering multiple targeted regimens would be necessary to effectively deplete the persister reservoirs in patients under cancer treatments.”DOI - https://doi.org/10.18632/oncotarget.28488Correspondence to - Cheuk Leung - ctleung@umn.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28488Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, persister cancer cells, cytostatic therapy, cancer recurrence, PTEN/PI3K/AKT, proteasome inhibitorAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- December 11, 2023 – A new #review paper was #published in Oncotarget's Volume 14 on December 1, 2023, entitled, “Risk factors for long-term arm morbidities following breast cancer treatments: A systematic review.”In this review, researchers Ifat Klein, Michael Friger, Merav Ben David, and Danit Shahar from Assuta Medical Center and Ben-Gurion University of the Negev in Israel aimed to examine the risk factors for arm morbidity following breast cancer treatments. The team took a broad view of all types of physical morbidity, including prolonged pain, lymphedema, decreased range of motion, and functional limitations.“A systematic literature review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines.”Studies exploring the risk factors for prolonged arm morbidity following breast cancer surgery and treatments were included. The studies were assessed independently according to pre-eligibility criteria, following data extraction and methodological quality assessment. 1,242 articles were identified. After removing duplicates, the full texts of 1,153 articles were examined. Sixty-nine of these articles met the criteria and were included in the review. These 69 articles identified 29 risk factors for arm morbidity following treatments for breast cancer. The risk of bias was evaluated using NIH study quality assessment tools. The studies reviewed were published between 2001 and 2021 and included a total of 22,886 patients who were followed up for between three months and 10 years. The main risk factors for long-term morbidity are removal of lymph nodes from the axilla, body mass index >30, having undergone a mastectomy, the stage of the disease, radiation therapy, chemotherapy, infection and trauma to the affected arm after surgery. “An understanding of the risk factors for prolonged arm morbidity after surgery can help doctors and therapists in making personalized decisions about the need and timing of rehabilitation treatments.”DOI - https://doi.org/10.18632/oncotarget.28539Correspondence to - Ifat Klein - ifatgoldberg@hotmail.comSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28539Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, risk factors, arm morbidity, physical rehabilitation, breast cancerAbout OncotargetOncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- December 6, 2023 – A new #researchpaper was #published in Oncotarget's Volume 14 on December 1, 2023, entitled, “Plasma levels of BCMA-positive extracellular vesicles correlate to response and side effects in myeloma patients treated with belantamab-mafodotin.”In myeloma patients, high levels of soluble B-cell maturation antigen (sBCMA) can limit the efficacy of BCMA-directed therapies. Belantamab-mafodotin is a BCMA antibody-drug conjugate and shows good overall response rates in heavily pretreated patients, but progression-free survival data are poor. In this new study, researchers Carsten Springer, Jürgen Krauter and Arne Trummer, from Städtisches Klinikum Braunschweig and Heidekreis-Klinikum in Germany, investigated whether sBCMA in blood plasma includes extracellular vesicles (EV) carrying BCMA or other myeloma antigens and if these BCMA-EV levels show a significant change during therapy with belantamab-mafodotin.“As the drug induces apoptosis, we hypothesized that sBCMA includes extracellular vesicles (EV) and thus evaluated numbers of BCMA-EV before and during belantamab therapy in 10 myeloma patients.”BCMA-EV were significantly higher in patients prior to Belantamab (median: 3227/μl; p = .013) than in other myeloma patients before therapy (n = 10; 1082/μl) or healthy volunteers (n = 10; 980/μl). During therapy, BCMA-EV showed a significant increase to a maximum of 8292/μl (p = .028). Maximal changes in BCMA-EV (Δmax = BCMA-EV at C1/maximal BCMA-EV) showed a strong inverse, logarithmic correlation (r = −.950; p < .001) with FLC ratio changes (Δmax = FLC ratio at C1/minimal FLC ratio) and BCMA-EV peaks often preceded FLC progression. Correlating increase of LDH and BCMA-EV levels, together with clinical symptoms, point to a mafodotin-induced eryptosis. In summary, BCMA-EV are a part of sBCMA, peak levels precede progression, and their measurement might be helpful in identifying resistance mechanisms and side effects of BCMA-targeted therapies.“To the best of our knowledge, we demonstrate for the first time that BCMA-positive extracellular vesicles can be found in blood plasma from myeloma patients and that BCMA expression on EV is 10 to 100 times higher than that of other well-known antigens of myeloma cells.”DOI - https://doi.org/10.18632/oncotarget.28538Correspondence to - Arne Trummer - arne.trummer@heidekreis-klinikum.deSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28538Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, myeloma, b cell maturation antigen, extracellular vesicles, belantamab-mafodotin, eryptosisAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- December 4, 2023 – A new #researchpaper was #published in Oncotarget's Volume 14 on December 1, 2023, entitled, “Osteopontin induces mitochondrial biogenesis in deadherent cancer cells.”Metastasizing cells display a unique metabolism, which is very different from the Warburg effect that arises in primary tumors. Over short time frames, oxidative phosphorylation and ATP generation are prominent. Over longer time frames, mitochondrial biogenesis becomes a pronounced feature and aids metastatic success. It has not been known whether or how these two phenomena are connected. In this new study, researchers Gulimirerouzi Fnu and Georg F. Weber from the University of Cincinnati’s James L. Winkle College of Pharmacy hypothesized that Osteopontin splice variants, which synergize to increase ATP levels in deadherent cells, also increase the mitochondrial mass via the same signaling mechanisms. “Here, we report that autocrine Osteopontin does indeed stimulate an increase in mitochondrial size, with the splice variant -c being more effective than the full-length form -a.” Osteopontin-c achieves this via its receptor CD44v, jointly with the upregulation and co-ligation of the chloride-dependent cystine-glutamate transporter SLC7A11. The signaling proceeds through activation of the known mitochondrial biogenesis inducer PGC-1 (which acts as a transcription coactivator). Peroxide is an important intermediate in this cascade, but surprisingly acts upstream of PGC-1 and is likely produced as a consequence of SLC7A11 recruitment and activation. In vivo, suppression of the biogenesis-inducing mechanisms leads to a reduction in disseminated tumor mass. “This study confirms a functional connection between the short-term oxidative metabolism and the longer-term mitochondrial biogenesis in cancer metastasis – both are induced by Osteopontin-c. The results imply possible mechanisms and targets for treating cancer metastasis.”DOI - https://doi.org/10.18632/oncotarget.28540Correspondence to - Georg F. Weber - georg.weber@uc.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28540Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, metastasis, metabolism, anchorage independence, mitochondrial mass, peroxideAbout OncotargetOncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Hair follicles are dynamic structures that undergo cyclic phases of growth, regression and quiescence. The growth phase, known as anagen, lasts for several years, followed by a short regression phase called catagen. During catagen, most cells within the follicle undergo programmed cell death, but a small population of stem cells remains viable to replenish the follicle during the subsequent growth phase. Understanding the mechanisms involved in hair follicle regression is not only important for elucidating normal tissue homeostasis but also for studying pathological conditions such as cancer and aging.In a recent study, researchers Bradley D. Keister, Kailin R. Mesa and Krastan B. Blagoev from the National Science Foundation, The Jane Coffin Childs Memorial Fund for Medical Research, Yale School of Medicine, Johns Hopkins University, Bulgarian Academy of Sciences, and Sorbonne Université shed light on the role of apoptotic cells in hair follicle regression and cell death. Their research paper was published in Oncotarget on October 19, 2023, entitled, “Apoptotic cells may drive cell death in hair follicles during their regression cycle.”“Here, we use a quantitative analysis of the length of hair follicles during their regression cycle.”Full blog - https://www.oncotarget.org/2023/11/29/can-mechanisms-of-hair-loss-shed-light-on-cancer-and-aging/Paper DOI - https://doi.org/10.18632/oncotarget.28529Correspondence to - Krastan B. Blagoev - kblagoev@nsf.govSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28529Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, hair follicle, stem cells, regression cycle, mathematical model, analysisAbout OncotargetOncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- November 28, 2023 – A new #editorial paper was #published in Oncotarget's Volume 14 on November 27, 2023, entitled, “The double-edge sword of CRISPR application for in vivo studies.”In this new paper, researcher Martin K. Thomsen from Aarhus University begins his editorial by discussing a hallmark paper that was published a decade ago by Platt et al. on the in vivo application of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) to generate cancer in different organs of mice. This hallmark paper outlines the advancement of delivering sgRNA’s to the target tissue to create loss or gain of function mutations without the need for timely intercrossing of genetic mouse strains. Furthermore, the study showed that multiplexing was possible, thereby enabling the method to target multiple sites simultaneously [1]. It was foreseen that this technology would change the way mouse models of cancer were generated, but even after 10 years, only few studies have relied on this methodology [2]. “The double-edged sword of in vivo application of CRISPR is the imperfection of mutations generated in the target sequence.” As CRISPR introduces mutations, they do not always occur, resulting in cells being present without the desired mutation. This is further complicated by the different types of indels, which can result in a functional protein with only changes in a few amino acids, without the introduction of a premature stop codon. This introduces clone-to-clone variation and results in tumors with a different mutation profile [3, 4]. However, this is also an advantage of CRISPR for generating in vivo cancer models as natural selection will occur, resulting in a cancer Darwinian evolution.“Altogether, the in vivo application of CRISPR will become more common, even though the technique has challenges, it will only become more feasible in the future, allowing more researchers to apply this technology.”DOI - https://doi.org/10.18632/oncotarget.28459Correspondence to - Martin K. Thomsen - mkt@biomed.au.dkSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28459Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, CRISPR, in vivo, mouse models, Adenoassociated virusAbout OncotargetOncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- November 27, 2023 – A recent #review paper was #published in Oncotarget's Volume 14 on July 1, 2023, entitled, “Targeting Ras with protein engineering.”Ras proteins are small GTPases that regulate cell growth and division. Mutations in Ras genes are associated with many types of cancer, making them attractive targets for cancer therapy. Despite extensive efforts, targeting Ras proteins with small molecules has been extremely challenging due to Ras’s mostly flat surface and lack of small molecule-binding cavities. These challenges were recently overcome by the development of the first covalent small-molecule anti-Ras drug, sotorasib, highlighting the efficacy of Ras inhibition as a therapeutic strategy. However, this drug exclusively inhibits the Ras G12C mutant, which is not a prevalent mutation in most cancer types. Unlike the G12C variant, other Ras oncogenic mutants lack reactive cysteines, rendering them unsuitable for targeting via the same strategy. In this review, researchers Atilio Tomazini and Julia M. Shifman from The Hebrew University of Jerusalem discuss protein engineering as a promising emergent method to target Ras, since engineered proteins have the ability to recognize various surfaces with high affinity and specificity. “While the development of small-molecule Ras inhibitors has been reviewed elsewhere [40], we focus our review on protein-based Ras inhibitors, describing the methods for their engineering, various scaffolds used for inhibitor design, and prospects for delivery of the designed Ras inhibitors into the cellular cytoplasm, where Ras is located.”Over the past few years, scientists have engineered antibodies, natural Ras effectors, and novel binding domains to bind to Ras and counteract its carcinogenic activities via a variety of strategies. These include inhibiting Ras-effector interactions, disrupting Ras dimerization, interrupting Ras nucleotide exchange, stimulating Ras interaction with tumor suppressor genes, and promoting Ras degradation. In parallel, significant advancements have been made in intracellular protein delivery, enabling the delivery of the engineered anti-Ras agents into the cellular cytoplasm. “These advances offer a promising path for targeting Ras proteins and other challenging drug targets, opening up new opportunities for drug discovery and development.”DOI - https://doi.org/10.18632/oncotarget.28469Correspondence to - Julia M. Shifman - jshifman@mail.huji.ac.ilSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28469Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - Ras oncogene, anti-Ras therapeutics, Ras targeting, protein engineering, protein designAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- November 22, 2023 – A new #research paper was #published in Oncotarget's Volume 14 on October 4, 2023, entitled, “Determination of genetic predisposition to early breast cancer in women of Kazakh ethnicity.”Breast cancer (BC) is the most common type of cancer among women in Kazakhstan. To date, little data are available on the spectrum of genetic variation in Kazakh women with BC.In this new study, researchers Gulnur Zhunussova, Nazgul Omarbayeva, Dilyara Kaidarova, Saltanat Abdikerim, Natalya Mit, Ilya Kisselev, Kanagat Yergali, Aigul Zhunussova, Tatyana Goncharova, Aliya Abdrakhmanova, and Leyla Djansugurova from the Institute of Genetics and Physiology, Kazakh Institute of Oncology and Radiology, Al-Farabi Kazakh National University, and Asfendiyarov Kazakh National Medical University aimed to identify population-specific genetic markers associated with the risk of developing early-onset BC and test their association with clinical and prognostic factors. “To our knowledge, this is the first study using NGS [next-generation sequencing] technology to study the genetic predisposition to early-onset BC women from Kazakhstan and assess their impact on the patients’ clinical outcomes.”The study included 224 Kazakh women diagnosed with BC (≤40 age). Entire coding regions (>1700 exons) and the flanking noncoding regions of 94 cancer-associated genes were sequenced from blood DNA using MiSeq platform. The researchers identified 38 unique pathogenic variants (PVs) in 13 different cancer-predisposing genes among 57 patients (25.4%), of which 6 variants were novel. In total, 12 of the 38 distinct PVs were detected recurrently, including BRCA1 c.5266dup, c.5278-2del, and c.2T>C, and BRCA2 c.9409dup and c.9253del that may be founder in this population. BRCA1 carriers were significantly more likely to develop triple-negative BC (OR = 6.61, 95% CI 2.44–17.91, p = 0.0002) and have family history of BC (OR = 3.17, 95% CI 1.14–8.76, p = 0.03) compared to non-carriers. “This study allowed the identification of PVs specific to early-onset BC, which may be used as a foundation to develop regional expertise and diagnostic tools for early detection of BC in young Kazakh women.”DOI - https://doi.org/10.18632/oncotarget.28518Correspondence to - Gulnur Zhunussova - gulnur_j@outlook.com, and Nazgul Omarbayeva - nomarbayeva1@gmail.comSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28518Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, breast cancer, early-onset breast cancer, triple negative breast cancer, next-generation sequencing, pathogenic variant, Kazakh populationAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- November 20, 2023 – A new editorial #paper was #published in Oncotarget's Volume 14 on August 30, 2023, entitled, “Predicting the molecular functions of regulatory genetic variants associated with cancer.”Some of inherited human genetic variation can contribute to important phenotypic diversity, such as the varying degrees of individual susceptibility to developing certain health conditions and individual response to therapeutic interventions. To date, over 490,000 genotype-phenotype associations have been discovered through large-scale genome-wide association studies (GWAS); however, molecular functions of most of these discovered GWAS variants remain unknown. In their recent editorial, researchers Jun S. Song and Mohith Manjunath from the University of Illinois at Urbana-Champaign discuss computational methods of genetic analysis using expression quantitative trait loci, frameworks for predicting regulatory genetic functions, application to transcription factors involved in cancer development and progression, and future implications for their methods in cancer research and precision medicine.“There are several technical challenges hindering our understanding [...].” First, the effect size of a typical genetic variant, as measured in terms of the odds ratio of genotype occurrence in case versus control populations, is very small, suggesting that macroscopic systems-level phenotypic differences modulated by each variant may also be small and difficult to detect. Next, most reported variants reside in non-protein-coding regions of the human genome, indicating that they are likely affecting the regulation of some unknown target genes’ expression. Finally, the discovered variants may not be functional themselves, but be merely in genetic linkage disequilibrium with other functional variants. “A promising approach to address these challenges is to integrate genomic, epigenomic, transcriptomic and machine learning methods to identify functional genetic variants and characterize their mode of action in regulating target genes.”DOI - https://doi.org/10.18632/oncotarget.28451Correspondence to - Jun S. Song - songj@illinois.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28451Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, genome-wide association studies, cancer risk, regulatory variants, functional genomicsAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Pancreatic ductal adenocarcinoma (PDA), a common type of pancreatic cancer, has proven to be largely resistant to immunotherapy, a treatment that uses the body’s immune system to fight cancer. Despite numerous successful pre-clinical trials using sophisticated PDA mouse models, clinical trials have failed to show a significant improvement in survival.In a recent editorial, researchers Brian Diskin, Sarah Schwartz and George Miller from Trinity Health of New England shed light on the complex interplay between the immune system and pancreatic cancer. Their paper was published in Oncotarget on April 24, 2023, and entitled, “The critical immune basis for differential responses to immunotherapy in primary versus metastatic pancreatic cancer.”Tumor Microenvironment and Liver Metastasis: Challenges in Pancreatic CancerThe authors attribute PDA immunotherapy resistance to the unique characteristics of the tumor microenvironment (TME). The TME is often hypoxic and fibrotic, making it inaccessible to immune cells. Furthermore, the immune cells that do infiltrate the TME often have tolerogenic features, meaning they are more likely to tolerate the presence of cancer cells rather than attack them.PDA most commonly metastasizes to the liver, an organ known for its immune tolerance. The liver is home to a diverse array of innate immune populations, including NK cells, Kupfer cells, NKT cells, and double negative T cells. Despite this, the liver is the most common location for metastasis from gastrointestinal cancers.“It is an unfortunate fact that all failed clinical trials assessing immunotherapeutic efficacy were conducted in metastatic PDA, whereas basic preclinical investigations are usually performed in primary PDA using genetically engineered mouse models. We postulated that this dichotomy may explain the gap between preclinical promise and ultimate clinical failure.”Full blog - https://www.oncotarget.org/2023/11/16/immunotherapy-response-in-primary-vs-metastatic-pancreatic-cancer/Paper DOI - https://doi.org/10.18632/oncotarget.28373Correspondence to - George Miller - gedalyamil@gmail.comSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28373Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, pancreatic cancer, liver metastasis, immunnotherapyAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- November 15, 2023 – A new #editorial paper was #published in Oncotarget's Volume 14 on March 31, 2023, entitled, “Obesity paradox and lung cancer, metformin-based therapeutic opportunity?”In their recent editorial, researchers Pedro Barrios-Bernal, Norma Hernández-Pedro, Luis Lara-Mejía, and Oscar Arrieta from Instituto Nacional de Cancerología discuss obesity, diabetes and lung cancer. Obesity is a complex multifactorial disease with detrimental effects on health. This disease induces a proinflammatory state, innate and adaptative immune system dysfunction, and immune exhaustion, which in conjunction promote cancer growth. Although obesity and type 2 diabetes mellitus (T2DM) have been associated with lung cancer (LC) development, several confounding factors, such as chronic inflammation, high insulin levels, microbiome, as well as the oncogenic potential of growth and sexual hormones, have introduced uncertainty and avoid the fully recognition of this relationship [1, 2]. Thus, therapies that can bring potential therapeutic effects to both comorbidities are being tested globally and their effect on cancer cells.“Altogether, there is a strong relationship between high BMI and increase survival in different LC stages and in combination with some anticancer therapies. Metformin has been shown to be a metabolism modifier that may adapt signaling pathways and immune sensitivity in tumor microenvironment.”DOI - https://doi.org/10.18632/oncotarget.28432Correspondence to - Oscar Arrieta - ogarrieta@gmail.comSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28432Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, obesity, lung cancer, metformin, tyrosine-kinase inhibitors, BMI, EGFR, obesity paradoxAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- November 13, 2023 – A new #editorial perspective was #published in Oncotarget's Volume 14 on March 11, 2023, entitled, “C/EBPβ cooperates with MYB to maintain the oncogenic program of AML cells.”In this new paper, researcher Karl-Heinz Klempnauer from Westfälische-Wilhelms-Universität discusses recent studies on the role of transcription factor MYB in acute myeloid leukemia (AML). MYB has been identified as a key regulator of a transcriptional program for self-renewal of AML cells. The MYB gene initially attracted attention as the progenitor of a retrovirally-transduced oncogene that induces a myeloid leukemia in chicken [1–4]. MYB encodes a transcription factor with essential roles in the development of the hematopoietic system [5] and the proliferation and differentiation of hematopoietic progenitor cells [6]. Subsequent work identified MYB also as a crucial player in the development and maintenance of leukemia in humans.“Recent work summarized here has now highlighted the CCAAT-box/enhancer binding protein beta (C/EBPβ) as an essential factor and potential therapeutic target that cooperates with MYB and coactivator p300 in the maintenance of the leukemic cells.”DOI - https://doi.org/10.18632/oncotarget.28377Correspondence to - Karl-Heinz Klempnauer - klempna@uni-muenster.deSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28377Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, MYB, C/EBPbeta, p300, GFI1, AMLAbout OncotargetOncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- November 8, 2023 – A new editorial #paper was #published in Oncotarget's Volume 14 on March 31, 2023, entitled, “Impact of SHP2 tyrosine phosphorylation on the development of acquired resistance to allosteric SHP2 inhibitors.”The SH2 domain-containing tyrosine phosphatase 2 (SHP2) is a ubiquitously expressed non-receptor protein tyrosine phosphatase, encoded by the PTPN11 gene. It is positively regulated by upstream receptor tyrosine kinases (RTKs) to activate downstream the RAS-ERK pathway. In this new editorial, researchers Giulia Franciosa and Jesper V. Olsen from the University of Copenhagen discuss potential leukemia therapies that effectively prevent adaptive resistance. Acute myeloid leukemia (AML) is a bone marrow malignancy characterized by a blockage of differentiation and an uncontrolled proliferation of myeloid hematopoietic progenitor cells. The internal tandem duplication (ITD) in the juxtamembrane domain of the RTK FLT3 is an oncogenic driver mutation that leads to constitutive activation of its tyrosine kinase activity. Consequently, FLT3 inhibitors that block its tyrosine kinase activity represent the targeted treatment option for patients with FLT3-ITD AML, often administrated in combination with induction chemotherapy. “Nevertheless, the short duration of remission urges the development of novel combinatorial therapies for FLT3-ITD AML.” Since 2016, several potent and selective allosteric, noncovalent SHP2 inhibitors have been developed and tested in clinical trials for solid tumors. A recent study reported the effectiveness of short-term treatment with the allosteric SHP2 inhibitor SHP099 as a single agent in clinically relevant mouse models of Flt3-ITD AML. This observation was in contrast with published data showing that allosteric SHP2 inhibition is only effective as combination treatment with inhibitors of other nodes of the RAS-ERK pathway. In a research article published by Pfeiffer et al., the Olsen’s lab at University of Copenhagen showed that two commercial FLT3-ITDpositive AML cell lines (MV-4-11 and MOLM-13) developed adaptive resistance after prolonged treatment in vitro with the allosteric SHP2 inhibitor SHP099.“All in all, the findings by Pfeiffer et al. suggest that combined inhibition of SHP2 and mutated RTKs are effective in preventing adaptive resistance, but also highlight the need for development of more potent and effective SHP2 inhibitors and combination therapies for clinical applications.”DOI - https://doi.org/10.18632/oncotarget.28392Correspondence to - Giulia Franciosa - giulia.franciosa@cpr.ku.dkSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28392Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, SHP2, PTPN11, tyrosine, phosphorylationAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- November 6, 2023 – A new #editorial paper was #published in Oncotarget's Volume 14 on October 31, 2023, entitled, “The uncharted role of HER2 mutant alleles in breast cancer.”Somatic HER2 mutations are a novel class of therapeutic targets across different cancer types. Treatment with the tyrosine kinase inhibitor (TKI) neratinib as a single agent continues to be evaluated in HER2-mutant metastatic disease. However, responses are heterogeneous, with frequent early progression. In this new editorial, researchers Rashi Kalra, Bora Lim, Matthew J. Ellis, and Shyam M. Kavuri from Baylor College of Medicine discuss the under-explored effects of individual HER2 mutant alleles on therapeutic response, a role for HER2 mutation in metastatic propensity, and differences in patient outcomes in ER+ invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC). The preclinical efficacy of additional agents is also discussed, particularly the pan-HER inhibitor poziotinib.“In summary, preclinical findings described above support clinical investigation of poziotinib in a subset of ER + mBC harboring HER2 somatic mutations and suggest further studies to evaluate poziotinib as a therapeutic agent in additional tumor types.”DOI - https://doi.org/10.18632/oncotarget.28489Correspondence to - Shyam M. Kavuri - meghashyam.kavuri@bcm.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28489Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, metastasis, poziotinib, HER2, neratinib, invasive lobular breast carcinomaAbout OncotargetOncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Extrahepatic biliary cancer is a specific type of biliary cancer that occurs outside the liver. It is considered rare, quite serious and often symptomless until later stages. The average age at diagnosis is 72. Extrahepatic biliary cancer typically involves the bile ducts, which carry bile from the liver and gallbladder to the small intestine. It can also involve the gallbladder, which plays a role in the digestion of fats by storing, concentrating and releasing bile as needed. One of the main genetic factors that contribute to biliary cancer is the mutation of Kras, a gene that regulates cell growth and division. Mutated Kras can cause cells to grow uncontrollably and form tumors. Another important genetic factor is the mutation of p53, a gene that normally acts as a guardian of the genome and triggers cell death or repair when DNA damage occurs. Mutated p53 can impair this function and allow cells to survive and accumulate more mutations.“[...] the exact role of p53 in the development of extrahepatic biliary cancer remains elusive.”In a new editorial paper, researchers Munemasa Nagao, Kenta Mizukoshi, Shinnosuke Nakayama, Mio Namikawa, Yukiko Hiramatsu, Takahisa Maruno, Yuki Nakanishi, Tatsuaki Tsuruyama, Akihisa Fukuda, and Hiroshi Seno from Kyoto University Graduate School of Medicine discussed their recent study exploring the role of p53 in preventing the development of extrahepatic biliary cancer. On March 31, 2023, their editorial was published in Oncotarget, entitled, "p53 protects against formation of extrahepatic biliary precancerous lesions in the context of oncogenic Kras."Full blog - https://www.oncotarget.org/2023/11/02/p53s-protective-role-in-extrahepatic-biliary-precancerous-lesions/Paper DOI - https://doi.org/10.18632/oncotarget.28380Correspondence to - Akihisa Fukuda - fukuda26@kuhp.kyoto-u.ac.jpSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28380Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, BilIN, ICPN, biliary cancer, Kras, p53About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- November 1, 2023 – A new research paper was published in Oncotarget's Volume 14 on October 31, 2023, entitled, “FAAH inhibition ameliorates breast cancer in a murine model.”Breast cancer is the leading cancer among females worldwide. Disease outcome depends on the hormonal status of the cancer and whether or not it is metastatic, but there is a need for more efficacious therapeutic strategies where first line treatment fails. In this new study, researchers Mallika Tripathy, Amy Bui, Jared Henderson, Jeffrey Sun, Christian Rutan Woods, Soumya Somani, Thao Doan, Anto Sam Crosslee Louis Sam Titus, and Chandra Mohan from the University of Houston’s Department Biomedical Engineering examined Fatty Acid Amide Hydrolase (FAAH) inhibition and endocannabinoids as therapeutic alternatives. “This study explores the functional relevance and therapeutic potential of FAAH inhibition combined with the proapoptotic activity of exogenous endocannabinoids on breast cancer survival.”FAAH is an integral membrane enzyme that hydrolyzes endocannabinoids, rendering them inactive, and FAAH inhibition is predicted to increase cancer cell death. To test this, breast cancer cells were probed for FAAH expression using Western blot analysis, treated with FAAH inhibitors, exogenous endocannabinoids, and combinations of the two treatments, and assessed for viability. High levels of FAAH were observed in different breast cancer cell lines. FAAH inhibition was more effective than exogenous endocannabinoid treatment, and the combination of FAAH inhibitors and endocannabinoids was the most effective in inducing apoptosis of breast cancer cells in vitro. In addition, in vivo FAAH inhibition reduced breast cancer growth in immunodeficient mice. Further research exploring the therapeutic potential and impact of FAAH expression on cancer cells is warranted.“FAAH inhibition is a promising approach, and tremendous progress has been made in the field to validate this mechanism as an alternative to chemotherapy.”DOI - https://doi.org/10.18632/oncotarget.28534Correspondence to - Chandra Mohan - cmohan@central.uh.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28534Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, FAAH, breast cancer, cancer therapy, apoptosisAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- October 30, 2023 – A new editorial paper was published in Oncotarget's Volume 14 on March 24, 2023, entitled, “Neutrophil PAD4: how does it function in cancer beyond promoting NETosis?”Expansion of pathologically activated immune suppressive myeloid cells called myeloid-derived suppressor cells (MDSC) is one of the hallmarks of cancer. In most tumor types, MDSC are represented primarily by pathologically activated neutrophils (PMN-MDSC). In this new editorial, researchers Laura Garcia-Gerique and Yulia Nefedova from the Wistar Institute discussed their team’s recent study identifying a novel mechanism by which neutrophil PAD4 promotes cancer progression. “Using several transplantable and genetically engineered mouse models, we demonstrated that tumor growth was accompanied by significantly elevated enzymatic activity of neutrophil PAD4 [10]. To further clarify the role of PAD4 in tumor progression, we utilized PAD4fl/fl MRP8Cre mice with targeted deletion of PAD4 in myeloid cells, primarily neutrophils.”PMN-MDSC originate in the bone marrow and migrate to various sites including tumor tissues and premetastatic niches. These cells have a relatively short lifespan (less than 48 hours) and, therefore, are continually replaced from the bone marrow. Tumor-infiltrating PMN-MDSC possess a potent suppressive activity as they are able to inhibit both antigen-specific immune responses of T cells and non-specific anti-CD3/CD28-stimulated responses. As a result, a highly immunosuppressive environment is created in tumors, which prevents their rejection via immunological mechanisms. In addition, PMN-MDSC employ non-immunological mechanisms to facilitate tumor progression, including angiogenesis, remodeling of extracellular matrix, and production of cytokines. In patients with solid tumors, levels of MDSC in circulation and tumor tissues have been positively associated with a poor response to the therapy in many types of cancer and represent an independent indicator of poor outcomes. However, many of the details about how PMN-MDSC support cancer progression, and thus approaches for therapeutically targeting these cells, remain enigmatic.“Taken together, our study identified a new mechanism responsible for transcriptional regulation of neutrophil migration and a new mechanism by which neutrophil PAD4 is contributing to tumor progression. PAD4 inhibitors are in development and may enter early phase clinical trials in the future.”DOI - https://doi.org/10.18632/oncotarget.28369Correspondence to - Yulia Nefedova - ynefedova@wistar.orgSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28369Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, PAD4, PMN-MDSC, neutrophils, neutrophil migrationAbout OncotargetOncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- October 25, 2023 – A new editorial perspective was published in Oncotarget's Volume 14 on March 24, 2023, entitled, “Genetic modifiers of p53: opportunities for breast cancer therapies.”Each day our cells encounter a wide range of genomic damage and the p53 protein arbitrates decisions of cell cycle arrest to allow repair of DNA or promote elimination of cells with malignant potential through apoptosis. In this new editorial perspective, researchers Prabin Dhangada Majhi, Aman Sharma and D. Joseph Jerry from the University of Massachusetts, Pioneer Valley Life Sciences Institute and Rays of Hope Center for Breast Cancer Research discuss TP53 mutations. The prevalence of TP53 mutations in nearly all tumors emphasizes its role as a formidable barrier that must be breached to allow oncogenic transformation. Inherited mutations in TP53 are also the primary genetic lesions found in Li-Fraumeni Syndrome (LFS), a familial cancer predisposition characterized by tumors in many tissues. However, tissues are not all equally vulnerable to disruptions in p53 function. Among women with inherited mutations in TP53, breast cancer is by far the most common tumor (Figure 1). Somatic mutations in TP53 are also prevalent in sporadic breast cancers, especially in the triple-negative subtype. The proportion rises to nearly 50% of breast cancers that exhibit impaired function of the p53 pathway based on gene expression signatures as a surrogate biomarker of p53 activity. Therefore, the breast epithelium appears to be uniquely sensitive to alterations in p53 function.“Genomewide association studies (GWAS) have identified over 300 polymorphisms that contribute to breast cancer risk [38–41]. These provide a rich resource of candidate polymorphisms that may modify the consequences of mutations in TP53.”DOI - https://doi.org/10.18632/oncotarget.28387Correspondence to - D. Joseph Jerry - jjerry@vasci.umass.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28387Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, p53, Li-Fraumeni syndrome, genetic modifiers, breast cancer, DNA repairAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- October 23, 2023 – A new research paper was published in Oncotarget's Volume 14 on October 19, 2023, entitled, “Apoptotic cells may drive cell death in hair follicles during their regression cycle.”Intravital microscopy in live mice has shown that the elimination of epithelial cells during hair follicle regression involves supra-basal cell differentiation and basal cell apoptosis through synergistic action of TGF-β (transforming growth factor) and mesenchymal-epithelial interactions. In this process the basal epithelial cells are not internally committed to death and the mesenchymal dermal papilla (DP) plays an essential role in death induction. Given that DP cells are not necessary for completion of the cycle, only for its initiation, it is still an open question as to the mechanism that leads to the propagation of apoptosis towards the regenerative stem cell population.In their new study, researchers Bradley D. Keister, Kailin R. Mesa and Krastan B. Blagoev from the National Science Foundation, The Jane Coffin Childs Memorial Fund for Medical Research, Yale School of Medicine, Johns Hopkins University, Bulgarian Academy of Sciences, and Sorbonne Université performed a quantitative analysis of the length of hair follicles to investigate their regression cycle. “In this paper we introduced a mathematical model of the hair follicle regression cycle that postulates that the regression is initiated by the dermal papilla, but that this signal affects only the cells adjacent to it.”The data are consistent with a propagation mechanism driven by apoptotic cells inducing apoptosis in their neighboring cells. The observation that the apoptosis slows down as the apoptotic front approaches the stem cells at the end of the follicle is consistent with a gradient of a pro-survival signal sent by these stem cells. An experiment that can falsify this mechanism is proposed.“In conclusion, hair follicle regression may be governed by cell-cell induced programmed cell death, which slows down as the stem cell compartment is approached and does not affect the stem cell compartment from which the growth phase is initiated. The class of models introduced here can be used to describe the renewal kinetics of other stem cell niches like the intestinal stem cell niche [18].”DOI - https://doi.org/10.18632/oncotarget.28529Correspondence to - Krastan B. Blagoev - kblagoev@nsf.govSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28529Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, hair follicle, stem cells, regression cycle, mathematical model, analysisAbout OncotargetOncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Hepatocellular carcinoma (HCC) is the most common type of liver cancer. It is particularly challenging to treat because HCC is often diagnosed in late stage and resistant to chemotherapy and radiation. However, advancements in targeted therapies and immunotherapies have opened new avenues for the treatment of this aggressive disease.In a new editorial paper, researchers Sawako Suzuki, Divya Venkatesh, Tomoaki Tanaka, and Carol Prives from Columbia University highlight the role of a metabolic enzyme known as glutamine synthase 2 (GLS2) in regulating ferroptosis in HCC. Ferroptosis is a form of cell death that involves iron-dependent accumulation of lipid peroxides. On October 19, 2023, their editorial was published in Oncotarget, entitled, “GLS2 shapes ferroptosis in hepatocellular carcinoma.”Full blog - https://www.oncotarget.org/2023/10/19/how-a-metabolic-enzyme-can-trigger-cell-death-in-liver-cancer-cells/Paper DOI - https://doi.org/10.18632/oncotarget.28526Correspondence to - Carol Prives - clp3@columbia.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28526Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, ferroptosis, hepatocellular carcinoma, GLS2, p53, tumor suppressionAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- October 19, 2023 – A new editorial paper was published in Oncotarget's Volume 14 on October 19, 2023, entitled, “GLS2 shapes ferroptosis in hepatocellular carcinoma.”In their new editorial, researchers Sawako Suzuki, Divya Venkatesh, Tomoaki Tanaka, and Carol Prives from Columbia University discuss ferroptosis regulation of GLS2 as a potential therapeutic strategy against liver diseases.“More than a decade has passed since our group (1) as well as Hu et al., (2) identified glutaminase (GLS2) as a p53 target gene that promotes the tricarboxylic acid cycle (TCA) via α-ketoglutarate (αKG) and lowers oxidative stress via increasing glutathione (GSH) [1, 2].” Two years after this Dixon et al., [3] described a form of cell death they named ferroptosis which is caused by iron-mediated lipid peroxidation. Then, three years later, Gao et al., reported that GLS2 but not GLS1 is an inducer of ferroptosis in human cancer cells [4]. Ferroptosis had first been shown to be regulated by p53 via repression of SLC7A11 [5]. The circle was closed by a study from the Murphy group who reported that a cancer-related nonsynonymous mutation in p53 (P47S) is correlated with failure to either activate GLS2 expression or produce ferroptosis [6]. “Our recent study (Suzuki et al.) [7] has validated the ability of GLS2 to promote ferroptosis in murine models.”DOI - https://doi.org/10.18632/oncotarget.28526Correspondence to - Carol Prives - clp3@columbia.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28526Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, ferroptosis, hepatocellular carcinoma, GLS2, p53, tumor suppressionAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- October 18, 2023 – A new editorial paper was published in Oncotarget's Volume 14 on April 14, 2023, entitled, “The nuclear envelope and metastasis.”In their new editorial, researchers Emily Hansen and James M. Holaska from Rowan University discuss nuclear morphology — one of the basic visual criteria used by pathologists to diagnose breast cancer. Immunofluorescence staining of the nuclear structural proteins lamin B and emerin was recommended as an effective diagnostic tool for both thyroid and breast cancer, suggesting nuclear structure is intimately tied to malignant transformation. But what role nuclear morphology plays in cancer transformation and progression remains unclear. “The most likely explanation for why cancer cells present with distinct nuclear morphology is thought to be related to the most likely route of cancer spread: the vasculature.”For a tumor to metastasize, cancer cells need to enter and exit the blood and lymphatic vessels by squeezing through extremely small gaps in the endothelium, most of which are 1.2–2 µm in diameter. While the cytoplasm is very flexible and the cytoskeleton can rearrange to fit through openings as narrow as 1 µm, the nuclear diameter (10–20 µm) and its considerable stiffness (2–10x stiffer than the cytoplasm) represent physical barriers to this process. “Thus, to enable metastasis, cancer cells must also increase their nuclear malleability.” Studies have shown that nuclear softening is associated with tumor aggressiveness and metastasis. Although nuclear softening is one of the ‘hallmarks of cancer’ it remains poorly understood. Nuclear shape and stiffness are governed by a complex set of structural proteins that serve as both scaffolds and signaling proteins to influence almost all aspects of nuclear function. The best studied nucleostructural proteins are lamins, which are frequently downregulated in cancer. However, it is difficult to ascertain whether specific functional consequences are due to lamins or due to displacement of lamin-interacting proteins upon lamin loss. For example, nuclear size and shape is also governed by emerin, which binds to lamins at the nuclear envelope (NE) and upon lamin loss is retained in the endoplasmic reticulum. Like lamins, emerin is frequently mutated in cancer, with mutations in its transmembrane and actin-binding domains. “We found that in breast cancer, emerin expression in tumor tissue is significantly correlated to survival time [16]. These data suggest emerin plays a central role in pathogenic transformation and progression of malignant breast tissue.”DOI - https://doi.org/10.18632/oncotarget.28375Correspondence to - James M. Holaska - holaska@rowan.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28375Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, emerin, metastasis, mechanotransduction, breast cancer, nucleoskeletonAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- October 17, 2023 – A new editorial paper was published in Oncotarget's Volume 14 on May 19, 2023, entitled, “GBP3-STING interaction in glioblastoma coordinates autophagy, anti-oxidative, and DNA repair programs in response to temozolomide.”In their recent editorial, researchers Jun Ma, Ziyu Wang, Clark C. Chen, and Ming Li from the University of Minnesota discussed the methylating agent, Temozolomide (TMZ). TMZ is the standard adjuvant chemotherapeutic drug for glioblastoma, which constitutes 17.7% of overall primary central nervous system tumors. The survival rate of this WHO Grade IV tumor has achieved a clinically significant prolongation of 2.5 months overall and an increase of 16.3% 2-year survival rate. However, one intractable challenge is the diverse reactions to temozolomide treatment. “The acquired resistance to the standard adjutant radiochemotherapy including temozolomide has favored the recurrence of some glioblastoma cases and has kept the milestone from moving forward for more than 15 years.”Guanylate-binding proteins (GBPs) are a group of dynamin-related large (~65 kDa) GTPases expressed in response to interferon and mediate intracellular immunity. Consisting of 7 members in humans, little is known about the function of GBPs beyond their role in innate cellular immunity. After recent years of dedication to the GBP family, its role in glioblastoma’s development and recurrence has drawn great attention. “More recently, Li’s lab did informatic analysis of clinically annotated glioblastoma datasets, laboratory studies of protein-protein interaction, and functional characterization after depletion or exogenous expression.”GBP family members such as GBP1, GBP2, GBP3, and GBP5 are highly elevated and play pro-tumor roles through multiple mechanisms in glioblastoma. Although other GBP family members did not show a prominent relationship with treatment resistance at the present stage, GBP3 showed significant up-regulation in response to temozolomide. Furthermore, it’s revealed that high levels of GBP3 expression in glioblastoma was associated with a worsened survival after temozolomide treatment. Consistent with this observation, exogenous expression of GBP3 induced temozolomide resistance in independent patient-derived glioblastoma neurosphere lines, while GBP3 silencing conferred temozolomide sensitivity, both in vitro and in vivo. “This sensitivity was associated with the accumulation of cytoplasmic DNA fragments, suggesting the involvement of Stimulator of interferon genes (STING).”DOI - https://doi.org/10.18632/oncotarget.28370Correspondence to - Ming Li - m2li@umn.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28370Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, GBP3, MGMT, glioblastoma, temozolomide resistance, STINGAbout OncotargetOncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Dr. Omkar Desai, from the Department of Surgery at Case Western Reserve University and University Hospitals Cleveland Medical Center, describes a research perspective he co-authored with Dr. Rui Wang that was published by Oncotarget in Volume 14, entitled, “HER3- A key survival pathway and an emerging therapeutic target in metastatic colorectal cancer and pancreatic ductal adenocarcinoma.”DOI - https://doi.org/10.18632/oncotarget.28421Correspondence to - Rui Wang - rxw517@case.eduAuthor video - https://www.youtube.com/watch?v=3-02jt7-MW8Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28421Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - HER3, colorectal, pancreatic cancer, metastasis, microenvironmentAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- October 11, 2023 – A new research paper was published in Oncotarget's Volume 14 on October 4, 2023, entitled, “Inhibiting BRAF/EGFR/MEK suppresses cancer stemness and drug resistance of primary colorectal cancer cells.”Drug resistance is a major barrier against successful treatments of cancer patients. Gain of stemness under drug pressure is a major mechanism that renders treatments ineffective. Identifying approaches to target cancer stem cells (CSCs) is expected to improve treatment outcomes for patients. In their new study, researchers Astha Lamichhane, Gary D. Luker, Seema Agarwal, and Hossein Tavana from The University of Akron, University of Michigan and Georgetown University aimed to elucidate the role of cancer stemness in resistance of colorectal cancer cells to targeted therapies.“[...] we developed spheroid cultures of patient-derived BRAFmut and KRASmut tumor cells and studied resistance mechanisms to inhibition of MAPK pathway through phenotypic and gene and protein expression analysis.”They found that treatments enriched the expression of CSC markers CD166, ALDH1A3, CD133, and LGR5 and activated PI3K/Akt pathway in cancer cells. The team examined various combination treatments to block these activities and found that a triple combination against BRAF, EGFR, and MEK significantly reduced stemness and activities of oncogenic signaling pathways. This study demonstrates the feasibility of blocking stemness-mediated drug resistance and tumorigenic activities in colorectal cancer.“Our approach to identify mechanisms of drug resistance of patient-derived cancer cells to targeted therapies and develop effective treatments is promising toward cancer precision medicine.”DOI - https://doi.org/10.18632/oncotarget.28517Correspondence to - Hossein Tavana - tavana@uakron.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28517Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, drug resistance, cancer stem cells, patient-derived tumor model, colorectal cancer, combination treatmentAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- October 9, 2023 – A new editorial perspective was published in Oncotarget's Volume 14 on October 4, 2023, entitled, “STAT3 as a biologically relevant target in H3K27M-mutant diffuse midline glioma.”Pediatric H3K27M-mutant diffuse midline gliomas (DMGs), including those formerly classified as diffuse intrinsic pontine gliomas (DIPG), are uniformly lethal central nervous system malignancies. Children diagnosed with these tumors have an extremely poor prognosis, with a median survival of approximately 12 months. The current standard of care for DMG includes possible biopsy for diagnostic confirmation and a 6-week course of palliative radiation. Despite enormous effort toward the development of novel therapeutics in DMG, chemotherapy remains ineffective in this disease. “Indeed, over 100 clinical trials for chemotherapeutics in DMG have failed to show therapeutic benefit [5].”In their new editorial perspective, researchers Jacob B. Anderson, Samantha M. Bouchal, Liang Zhang, and David J. Daniels from the Mayo Clinic discussed the currently available literature and their recent study on the Signal Transducer and Activator of Transcription (STAT) as a biologically relevant therapeutic target in H3K27M-mutant DMGs. In their recently published manuscript, the lab performed a screen of drugs currently in clinical use or clinical trials for efficacy against a library of H3K27Mmutant and H3-wildtype patient-derived cell lines. The results of this drug screen identified the STAT3 signaling pathway as a novel target in DMG.“Until recently, however, STAT3 was not a druggable target.”DOI - https://doi.org/10.18632/oncotarget.28516Correspondence to - David J. Daniels - daniels.david@mayo.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28516Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, H3K27M, DMG, DIPG, midline glioma, STAT3About OncotargetOncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Breast cancer (BC) is one of the most common and deadly cancers worldwide, affecting millions of women every year. However, not all women share the same risk of developing breast cancer. There are many factors that influence this disease, including age, lifestyle, family history, and genetic makeup.One of the most important aspects of breast cancer research is to identify the genetic factors that predispose some women to develop breast cancer at an early age, especially in different ethnic groups that may have unique genetic variants. This can help to improve the prevention, diagnosis and treatment of breast cancer, as well as to reduce the health disparities among different populations.In a new study, researchers Gulnur Zhunussova, Nazgul Omarbayeva, Dilyara Kaidarova, Saltanat Abdikerim, Natalya Mit, Ilya Kisselev, Kanagat Yergali, Aigul Zhunussova, Tatyana Goncharova, Aliya Abdrakhmanova, and Leyla Djansugurova from the Institute of Genetics and Physiology, Kazakh Institute of Oncology and Radiology, Al-Farabi Kazakh National University, and Asfendiyarov Kazakh National Medical University aimed to determine the genetic predisposition to early breast cancer in women from Kazakhstan — a population that has not been well studied before. On October 4, 2023, their research paper was published in Oncotarget, entitled, “Determination of genetic predisposition to early breast cancer in women of Kazakh ethnicity.”“Our study may reveal previously uncharacterized population-specific variants that may increase the risk of BC in the Kazakh population.”Full blog - https://www.oncotarget.org/2023/10/05/genetic-insights-into-early-breast-cancer-in-kazakhstan/Paper DOI - https://doi.org/10.18632/oncotarget.28518Correspondence to - Gulnur Zhunussova - gulnur_j@outlook.com, and Nazgul Omarbayeva - nomarbayeva1@gmail.comSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28518Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, breast cancer, early-onset breast cancer, triple negative breast cancer, next-generation sequencing, pathogenic variant, Kazakh populationAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- October 4, 2023 – A new review paper was published in Oncotarget's Volume 14 on September 28, 2023, entitled, “UDP-glucose dehydrogenase (UGDH) in clinical oncology and cancer biology.”UDP-glucose-6-dehydrogenase (UGDH) is a cytosolic, hexameric enzyme that converts UDP-glucose to UDP-glucuronic acid (UDP-GlcUA), a key reaction in hormone and xenobiotic metabolism and in the production of extracellular matrix precursors. In this review, researchers Meghan J. Price, Annee D. Nguyen, Jovita K. Byemerwa, Jasmine Flowers, César D. Baëta, and C. Rory Goodwin from Johns Hopkins Hospital, Duke University, Stanford University, Duke Center for Brain and Spine Metastasis, and Duke Cancer Institute classify UGDH as a molecular indicator of tumor progression in multiple cancer types, describe its involvement in key canonical cancer signaling pathways, and identify methods to inhibit UGDH, its substrates, and its downstream products. “As such, we position UGDH as an enzyme to be exploited as a potential prognostication marker in oncology and a therapeutic target in cancer biology.”DOI - https://doi.org/10.18632/oncotarget.28514Correspondence to - C. Rory Goodwin - rory.goodwin@duke.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28514Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, UDP-6 glucose dehydrogenase, UGDH, oncology, cancer biologyAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- October 3, 2023 – A new editorial paper was published in Oncotarget's Volume 14 on September 25, 2023, entitled, “DISE, an ancient anti-cancer mechanism that senses mutational load in cancerous cells?”In their new editorial, researchers Monal Patel and Marcus E. Peter from Northwestern University discuss a recent breakthrough in cancer therapy. Despite the multiple advances in therapy, cancer remains one of the most common causes of death globally. It is a systemic disease affecting people of all ages and originates at the level of single cells which, upon acquisition of mutations, become neo-plastically transformed.Cell division is the biggest risk factor for the accumulation of mutations, explaining why all multicellular organisms which evolved about 2 billion years ago, are prone to cancer. Given the recent achievements in cancer treatment with immune checkpoint blockade therapies, multicellular organisms may have developed the immune system as a mechanism to eradicate cancerous cells. “However, the immune system arose relatively recent, ~500 million years ago [3].” Moreover, studies have shown that cancer cells can become resistant to the anticancer activity of both the innate and the adaptive immune system. Therefore, while the immune system is important, it is likely not the most vital machinery that emerged in multicellular organisms to prevent cancer formation. The researchers believe that there are other more effective and archaic anti-cancer mechanisms that are conserved during evolution. Of note, RNA interference (RNAi) is a highly conserved biological mechanism for silencing gene expression. While RNAi likely emerged as a defense tool against viruses and other foreign nucleic acids, it has also evolved to have other activities in the cells. The team’s research has identified a new evolutionarily conserved RNAi-based form of cell death that targets essential survival genes: Death Induced by Survival gene Elimination (DISE).“DISE was discovered through our work on CD95 and its ligand, CD95L, where we found that more than 80% of 26 different short interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs) derived from the two genes, killed multiple cancer cell lines via simultaneous activation of multiple cell death pathways; and we were unable to find a way to inhibit this form of cell death [9].”DOI - https://doi.org/10.18632/oncotarget.28466Correspondence to - Marcus E. Peter - m-peter@northwestern.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28466Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, cell death, evolution, RNAi, short RNAsAbout OncotargetOncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- September 27, 2023 – A new editorial paper was published in Oncotarget's Volume 14 on September 22, 2023, entitled, “Reassessing the risks and benefits of COVID-19 precautions in 2023.”The COVID-19 pandemic has killed over one million Americans with many dying during the Omicron wave. By now most Americans have either had COVID-19 and/or been vaccinated against it. Despite the availability of updated immunizations, only 16.7% of Americans are now up-to-date on bivalent boosters. In their new editorial, researchers Thomas A. Ollila, Rashida Taher and Prashanth Moku from the Alpert Medical School of Brown University and Rhode Island Hospital discuss the current state of COVID-19 treatment.“At our cancer center, we treat many patients with hematologic malignancies, most of whom are older adults.”Patients with hematologic malignancies, especially lymphoma, are at increased risk of poor response to vaccination and worse outcomes from COVID-19 infection. The researchers state that most of their patients have been abundantly cautious since the onset of the pandemic and some have avoided ever becoming infected. Patients in their clinic frequently inquire about the safety of being outdoors, spending time with their families during large gatherings (Christmas, Thanksgiving, etc.), and methods to prevent the contraction of COVID-19. “Despite these precautions, too many patients reached remission from cancer only to then perish from COVID-19 in the first years of the pandemic.”The concerns behind their questions are very real, but understanding how to best answer them is not always easy and their abundance of caution is not without cost. Grandchildren’s birthdays went uncelebrated, weddings were forgone, and memorable moments with loved ones were lost. With both aging and malignancy, an acute awareness of the limited days means that there may not be years ahead to make up for all that was missed. “Although COVID-19 continues to pose a serious threat, medical advancements have now allowed for a more in-depth risk-benefit discussion to weigh the risk of infection versus the challenges of social isolation.”DOI - https://doi.org/10.18632/oncotarget.28468Correspondence to - Thomas A. Ollila - thomas_ollila@brown.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28468Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, COVID, immunosuppression, coronavirus, vaccination, lymphomaAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- September 25, 2023 – A new research paper was published in Oncotarget's Volume 14 on September 22, 2023, entitled, “Transcriptomic analysis identifies four novel receptors potentially linking endometrial cancer with polycystic ovary syndrome and generates a transcriptomic atlas.”Polycystic Ovary Syndrome (PCOS) is associated with a 3 to 4-fold increased risk of endometrial cancer (EC), but molecular mechanisms are unclear. Upregulation of the IGF1 gene in PCOS endometrium may increase EC risk, but this is uncertain. In this new study, researchers Fatma Alqutami, Mahmood Hachim, Charlie Hodgman, and William Atiomo from the Mohammed Bin Rashid University of Medicine and Health Sciences and the University of Nottingham aimed to investigate links between EC and PCOS, by analyzing publicly available transcriptomic data. “The original aim of this study was to investigate the links between EC and PCOS, by analysing publicly available transcriptomic data and investigate IGF-1 and IGFBP gene expression in the endometrium of women with PCOS and EC compared with normal endometrium.”The NCBI Gene Expression Omnibus was used to identify relevant studies. Differentially expressed genes (DEGs) were identified and analyzed using Metascape to identify pathways of interest. PCOS DEGs that encode proteins secreted into blood were identified using the Human Protein Atlas blood protein database. EC DEGs that are cellular receptors were identified using EcoTyper. These were intersected to identify which EC receptors interact with PCOS secreted proteins. Seven receptors were identified in EC but only PTPRF, ITGA2, ITGA3, and ITGB4 genes were expressed on epithelial cells. Pathway enrichment of these genes showed that the major and common pathway involved was that of the PI3K-AKT signaling pathway which was consistent with a link between PCOS and EC. However, IGF1 was down regulated in PCOS and EC. “Our conclusions at this stage do not support a link between IGF-1 and IGFBP genes in PCOS and EC. However, we have identified four novel receptors which may underpin the risk of EC in PCOS, and we believe our findings provide sufficient evidence to form the basis for a transcriptomic atlas to underpin future research into the links between PCOS and EC and the molecular mechanisms underpinning both diseases.”DOI - https://doi.org/10.18632/oncotarget.28513Correspondence to - William Atiomo - william.atiomo@mbru.ac.aeSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28513Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, polycystic ovary syndrome, endometrial cancer, transcriptomics, IGF1, in-silicoAbout OncotargetOncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Multiple myeloma (MM) is a type of blood cancer that affects plasma cells, which are responsible for producing antibodies. MM is characterized by the accumulation of abnormal plasma cells in the bone marrow, leading to bone damage, kidney failure, anemia, and increased susceptibility to infections. MM is a heterogeneous disease with different subtypes and genetic mutations that affect the prognosis and response to treatment. Therefore, there is a need for new biomarkers and therapeutic targets that can improve the outcomes of MM patients.One of the potential targets that has recently emerged is the fatty acid binding protein (FABP) family. FABPs are proteins that bind and transport fatty acids, which are essential for energy production, cell signaling and membrane synthesis. FABPs are expressed in various tissues and organs, and have different roles depending on their location and type. There are nine members of the FABP family, but FABP5 seems to be the most relevant for MM.In a recent editorial paper, researchers Heather Fairfield and Michaela R. Reagan from Maine Health Institute for Research, University of Maine and Tufts University School of Medicine summarized previous findings from their 2023 study and the current evidence on the role of FABPs in MM. On June 19, 2023, their editorial was published in Oncotarget, entitled, “The hope for targeting fatty acid binding proteins in multiple myeloma.”Full blog - https://www.oncotarget.org/2023/09/21/targeting-fatty-acid-binding-proteins-in-multiple-myeloma/Paper DOI - https://doi.org/10.18632/oncotarget.28437Correspondence to - Michaela R. Reagan - Michaela.Reagan@mainehealth.orgSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28437Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, multiple myeloma, FABPs, fatty acid binding proteins, immunoncology, pre-clinical discoveryAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- September 20, 2023 – A new editorial paper was published in Oncotarget's Volume 14 on September 15, 2023, entitled, “Potential repurposing of DPP4 inhibitors for target therapy resistance in renal cell carcinoma.”In their new editorial, researchers Kuniko Horie and Satoshi Inoue from Saitama Medical University and Tokyo Metropolitan Institute for Geriatrics and Gerontology discuss renal cell carcinoma (RCC) — a major adult kidney cancer, which is often incidentally discovered as an asymptomatic disease on imaging in the developed countries. RCC has the most fatal disease among urological cancers, as a recent 5-year relative survival rate in the U.S. (2009–2015) is less than 80%. While RCC is known as a cancer resistant to chemo- and radio-therapies, the prognosis of RCC has been remarkably improved after the clinical application of tyrosine kinase inhibitors (TKIs) and immunotherapy. The rationale for the efficacy of TKIs in RCC is mainly based on the angiogenetic status, particularly in clear cell RCC (ccRCC) that is the most common type of RCC (70–75% of RCC), in which the loss of function mutation of Von Hippel-Lindau (VHL) tumor suppressor gene activates hypoxia inducible factor (HIF) and vascular endothelial growth factor (VEGF) pathways. The first-line TKIs that predominantly target VEGF receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) (e.g., sunitinib and sorafenib) have been clinically used since late 2000s, and the second-line TKIs such as cabozantinib, which targets more receptor tyrosine kinases including MET and TAM kinases as well as VEGFR, have been further applied to the treatment of advanced RCC since early 2010s in which the first-line TKIs are ineffective.“In our recent study, we established a panel of patient-derived ccRCC spheroid cultures with the enhancement of cancer stemness gene signature including DPP4 [9]. Focusing on TKI sunitinib sensitivity, we demonstrated that DPP4 inhibition increased sunitinib efficacy in DPP4-high RCC spheroids and DPP4 was upregulated in sunitinib-resistant RCC cells.”DOI - https://doi.org/10.18632/oncotarget.28463Correspondence to - Satoshi Inoue - sinoue07@gmail.comSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28463Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, renal cell carcinoma (RCC), tyrosine kinase inhibitor (TKI), Dipeptidyl peptidase IV (DPP4), drug resistance, drug repurposingAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
BUFFALO, NY- September 19, 2023 – A new research paper was published in Oncotarget's Volume 14 on September 15, 2023, entitled, “Real time ex vivo chemosensitivity assay for pancreatic adenocarcinoma.”Patient-derived organoids (PDOs) and xenografts (PDXs) have been extensively studied for drug-screening. However, their usage is limited due to lengthy establishment time, high engraftment failure rates and different tumor microenvironment from original tumors. In this new study, researchers Dae Won Kim, Francisca Beato, Youngchul Kim, Alexandra F. Tassielli, Ruifan Dai, Jason W. Denbo, Pamela J. Hodul, Mokenge P. Malafa, and Jason B. Fleming from Moffitt Cancer Center developed real time-live tissue sensitivity assay (RT-LTSA) using fresh tumor samples to overcome these limitations.“To overcome the major hurdles of the PDX-based assay, we developed real time LTSA (RT-LTSA) using fresh tumor samples. In this study, we report a reliable and reproducible RT-LTSA with resected fresh tumor samples to predict patients’ clinical response to chemotherapy in pancreatic cancer.”Tissue slices from resected pancreatic cancer samples were placed in 96-well plates, and the slices were treated with chemotherapeutic agents. The correlation between the chemo-sensitivity of tissue slices and each patient’s clinical outcome was analyzed. The viability and tumor microenvironment of the tissue slices were well-preserved over 5 days. The drug sensitivity assay results were available within 5 days after tissue collection. While all 4 patients who received RT-LTSA sensitive adjuvant regimens did not develop recurrence, 7 of 8 patients who received resistant adjuvant regimens developed recurrence. The researchers observed significantly improved disease-free survival in the patients who received RT-LTSA sensitive adjuvant regimens (median: not reached versus 10.6 months, P = 0.02) compared with the patient who received resistant regimens. A significant negative correlation between RT-LTSA value and relapse-free survival was observed (Somer’s D: −0.58; P = 0.016).“RT-LTSA which maintains the tumor microenvironment and architecture as found in patients may reflect clinical outcome and could be used as a personalized strategy for pancreatic adenocarcinoma. Further, studies are warranted to verify the findings.”DOI - https://doi.org/10.18632/oncotarget.28508Correspondence to - Jason B. Fleming - jason.fleming@moffitt.orgSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28508Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, pancreatic cancer, sensitivity assay, chemotherapyAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/X - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new editorial paper was published in Oncotarget's Volume 14 on July 7, 2023, entitled, “Systemic treatment for brain metastasis in HER2- positive advanced breast cancer: what have we learned so far?”
In their new editorial, researchers Marta Vaz Batista, José Perez-Gracia, Inês Eiriz, Maria Gion, Antonio Llombart, Sofia Braga, and Javier Cortés from Medica Scientia Innovation Research (MEDSIR) and Hospital Professor Doutor Fernando Fonseca discuss new drugs available for breast cancer (BC) patients with brain metastasis (BM). The better survival of Human Epidermal growth factor receptor-type 2 positive (HER2+) BC patients unmasked the biological predilection of this BC subtype for development of BM.
Indeed, central nervous system (CNS) is a frequent metastatic site for HER2+ advanced BC patients. Over the last years, new therapeutic strategies targeting the HER2 protein have been introduced for systemic treatment of HER2+ BC - either tyrosine kinase inhibitors, monoclonal antibodies, or antibody-drug conjugates. Patients with BMs have a poorer outcome, compared with patients without BMs, but their prognosis is also improving with the introduction of new anti HER2+ - targeted therapies.
“Our group has been working in the DEBBRAH trial, using trastuzumab deruxtecan for different settings of CNS involvement: stable or progressing BM and/or leptomeningeal carcinomatosis.”
The team included patients with HER2+ and HER2-low BC. Activity of trastuzumab-deruxtecan in patients with HER2+ BC and untreated or progressing after local therapy BMs also has been shown in another phase II trial.
“The final results are yet to be reported, but so far, we observed intracranial responses in HER2+ BC patients [7].”
Read the full editorial: DOI: https://doi.org/10.18632/oncotarget.28435
Correspondence to: Marta Vaz Batista - marta.vaz@hff.min-saude.pt
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28435
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - cancer, brain metastasis, HER2+ breast cancer
About Oncotarget
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new editorial paper was published in Oncotarget's Volume 14 on May 26, 2023, entitled, “Latest updates on MET targeted therapy for EXON 14 mutations in lung cancer.”
In their new editorial, researchers Mira Al Jaberi, Wolfgang Clough and Samir Dalia from Mercy Hospital discuss the MET gene. Several alterations in the MET gene were identified as targetable oncogenic changes leading to non-small cell lung cancer (NSCLC). These include genomic amplifications, exon 14 skipping mutations and fusion.
Capmatinib has been considered as a first-line treatment for patients with NSCLC carrying a MET exon 14 skipping mutation since May 2020 by the USFDA. A study newly published in early 2023 showed that Crizotinib, a tyrosine kinase inhibitor, was also effective for MET fusions, which occur rarely in 0.2–0.3% of patients with lung cancer. A major challenge arising after the introduction of tyrosine kinase inhibitors is limited clinical benefit, which is due to primary and potential secondary acquired drug resistance.
“A major challenge arising after the introduction of tyrosine kinase inhibitors is limited clinical benefit, which is due to primary and potential secondary acquired drug resistance [4, 5].”
Several structurally different MET tyrosine kinase inhibitors (TKIs) have been developed or are under clinical evaluation. TKIs are categorized into type I TKIs (type Ia: crizotinib; type Ib: savolitinib, capmatinib) and type II TKIs (cabozantinib, glesatinib, merestinib). Combination therapy reduces resistance and enhances clinical outcomes.
“These clinical trials along with others will show us if other MET inhibitors or combination therapy may be better than the current standard of care.”
DOI - https://doi.org/10.18632/oncotarget.28419
Correspondence to - Samir Dalia - samir.dalia@mercy.net
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28419
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - cancer, non small cell lung cancer, MET mutation, targeted therapy, precision medicine
About Oncotarget
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
How can we understand the role of genetic variations in cancer development and treatment? This is one of the most challenging and important questions in modern biology and medicine. A new editorial paper, by researchers Jun S. Song and Mohith Manjunath from the University of Illinois at Urbana-Champaign, offers a novel discussion involving computational methods to address this question. On August 30, 2023, their editorial was published in Oncotarget, entitled, "Predicting the molecular functions of regulatory genetic variants associated with cancer." In this editorial, the authors review recent advances and challenges in identifying and characterizing the functional effects of genetic variants that affect gene regulation, such as enhancers, promoters, and transcription factors. These variants, also known as expression quantitative trait loci (eQTLs), can modulate the expression levels of genes and influence various cellular processes and phenotypes, including cancer susceptibility and response to therapy.The authors propose a framework for predicting the molecular functions of eQTLs based on their genomic context, epigenetic marks, chromatin accessibility, and three-dimensional interactions. They also discuss how to integrate multiple types of data and methods to improve the accuracy and interpretability of the predictions. Furthermore, they highlight the potential applications and implications of their approach for cancer research and precision medicine.“A promising approach to address these challenges is to integrate genomic, epigenomic, transcriptomic and machine learning methods to identify functional genetic variants and characterize their mode of action in regulating target genes.”Full blog - https://www.oncotarget.org/2023/09/07/predicting-functions-of-cancer-associated-genetic-variants/Editorial DOI - https://doi.org/10.18632/oncotarget.28451Correspondence to - Jun S. Song - songj@illinois.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28451Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, genome-wide association studies, cancer risk, regulatory variants, functional genomicsAbout Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new editorial paper was published in Oncotarget's Volume 14 on August 30, 2023, entitled, “Subpopulations of AIB1 isoform-expressing breast cancer cells enable invasion and metastasis.”In their new editorial, researchers Amber J. Kiliti, Ghada M. Sharif, Anton Wellstein, and Anna T. Riegel from Georgetown University Medical Center discuss potential mechanisms of breast cancer invasion and metastasis. Genetic and epigenetic events drive individual tumor cells to proliferate and expand into a heterogeneous mixture of cells that evade immune surveillance, acquire the ability to invade the vasculature and spread as metastatic seeds to distant sites. Organ metastasis contributes to more than 90% of all cancer-related deaths. “The model of Darwinian evolution explains the stepwise selection of cancer cells capable of invasion and metastatic spread and an extensive body of work supports that cancer cell-autonomous features match the selected cancer cell ‘seed’ with the appropriate ‘soil’ of the target organ.”However, this concept was challenged in a recent paper in Cancer Research. Sharif et al. observed that a subclonal population of cells in a heterogeneous tumor can significantly alter the growth characteristics, invasiveness and metastasis of an entire tumor through cell-cell crosstalk. These functionally relevant cell subpopulations are difficult to detect through bulk analysis though their presence may influence disease outcome and efficacy of treatments. “In their paper, Sharif et al. detailed how expression of a splice isoform of the transcriptional coregulator and oncogene Amplified In Breast Cancer 1 (AIB1) in a small subpopulation of cells can lead to increased tumor growth and invasion of surrounding tissues by ductal carcinoma in situ (DCIS) cells.”DOI - https://doi.org/10.18632/oncotarget.28452Correspondence to - Anna T. Riegel - ariege01@georgetown.eduVideo short - https://www.youtube.com/watch?v=_yZnwzitBekSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28452Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, AIB1, AIB1Δ4, breast cancer, invasion, metastasisAbout OncotargetOncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research paper was published in Oncotarget's Volume 14 on August 30, 2023, entitled, “Analytic validation of NeXT Dx™, a comprehensive genomic profiling assay.”
In this new research paper, researchers from Personalis, Inc. describe the analytic validation of NeXT Dx, a comprehensive genomic profiling assay to aid therapy and clinical trial selection for patients diagnosed with solid tumor cancers.
“The NeXT Dx clinical report currently provides the ordering clinician with information from 401 cancer-related genes on clinically relevant mutations, as well as related drug response associations and a curated list of clinical trials that may be applicable to the patient.”
Proprietary methods were utilized to perform whole exome and whole transcriptome sequencing for detection of single nucleotide variants (SNVs), insertions/deletions (indels), copy number alterations (CNAs), and gene fusions, and determination of tumor mutation burden and microsatellite instability. Variant calling is enhanced by sequencing a patient-specific normal sample from, for example, a blood specimen. This provides highly accurate somatic variant calls as well as the incidental reporting of pathogenic and likely pathogenic germline alterations. Fusion detection via RNA sequencing provides more extensive and accurate fusion calling compared to DNA-based tests.
NeXT Dx features the proprietary Accuracy and Content Enhanced technology, developed to optimize sequencing and provide more uniform coverage across the exome. The exome was validated at a median sequencing depth of >500x. While variants from 401 cancer-associated genes are currently reported from the assay, the exome/transcriptome assay is broadly validated to enable reporting of additional variants as they become clinically relevant. NeXT Dx demonstrated analytic sensitivities as follows: SNVs (99.4%), indels (98.2%), CNAs (98.0%), and fusions (95.8%). The overall analytic specificity was >99.0%.
“By more comprehensively characterizing the molecular characteristics of each patient’s tumor, NeXT Dx provides personalized recommendations critical to clinical decision-making with respect to current FDA-approved drug-variant specific treatments and evolving treatment opportunities via enrollment in clinical trials.”
DOI - https://doi.org/10.18632/oncotarget.28490
Correspondence to - Richard Chen - richard.chen@Personalis.com
Video short - https://www.youtube.com/watch?v=YnKfcj6R36U
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28490
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - cancer, comprehensive genomic profiling, whole exome sequencing, whole transcriptome sequencing, tumor-normal, precision medicine
About Oncotarget
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new research perspective was published in Oncotarget's Volume 14 on April 14, 2023, entitled, “Adopted neoplastic cells and the consequences of their existence.”
In this research perspective, researcher Yuri Lazebnik from Lerna Consulting begins by explaining a view that guides the bulk of cancer research and oncology: each neoplastic cell in a tumor is a genetic offspring of another neoplastic cell.
“Yet, analyzing tumors from transplant patients has revealed that some normal migratory cells adopt the phenotype of neoplastic cells without acquiring their genome, thus becoming what I suggest to call adopted neoplastic cells.”
This commentary reviews the evidence for the existence of adopted neoplastic cells, outlines the consequences of their presence, and discusses what kind of cells can be adopted, how and why.
“Finally, as experiments with humans can go only that far, and fortunately so, testing the hypotheses we have discussed will require experimental systems, such as human tumor explants which have been explored to reveal intercellular bridging [129, 130] and chimeric animals designed to monitor cell fate, cell fusion, and component transfer [206].”
DOI - https://doi.org/10.18632/oncotarget.28408
Correspondence to - Yuri Lazebnik - yuri@lernaconsulting.com
Video short - https://www.youtube.com/watch?v=THtJfHLi_FM
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28408
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - cancer, tumor microenvironment, horizontal oncogenesis, intercellular bridges, cell fusion, cell repair
About Oncotarget
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Dr. Mangesh A. Thorat from Guy’s Hospital in London, Queen Mary University of London, and King’s College London, describes a recent #editorial he authored that was #published by Oncotarget in Volume 14, entitled, “Multiclonality of ER expression in DCIS – Implications for clinical practice and future research.” #author #interview #authorinterview #researcher #cancer #cancerresearch #breastcancer #research #recurrence #clonality #ductalcarcinoma #ER #openaccess #openscience #peerreview #journal #publication #meded #publishing #researcher #video
DOI - https://doi.org/10.18632/oncotarget.28450
Correspondence to - Mangesh A. Thorat - thoratmangesh@gmail.com; m.thorat@qmul.ac.uk
Video interview - https://www.youtube.com/watch?v=TGeiFcKjbaQ
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28450
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - cancer, ductal carcinoma in situ (DCIS), invasive breast cancer, ER, recurrence, clonality
About Oncotarget
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new editorial paper was published in Oncotarget's Volume 14 on June 6, 2023, entitled, “A macrophage is a macrophage is a macrophage—in metastasis.”
In this new editorial, researcher Thomas T. Tapmeier from Monash University, Hudson Institute of Medical Research and University of Oxford discusses a recent study he co-authored on how lung macrophages evolve during metastatic growth of lung colonies in a mouse model of melanoma. Macrophages have important roles in the response to infection or injury and can orchestrate the appropriate response after sampling their microenvironment, devouring anything untoward and presenting ingested antigens to T cells to elicit an adaptive immune response. In adult life, they develop from bone marrow-derived precursors and circulating monocytes, which differentiate into macrophages within tissue.
“Apart from their role in clearing challenges to tissue integrity, macrophages have an essential role in growth-related processes such as angiogenesis and vascular remodelling, neural patterning, and ductal growth of developing glands [2].”
However, their powers can be usurped by tumors, which cannot grow beyond a certain size or metastasis without the help of macrophages. This is crucial, as the primary tumor might be amenable to treatment—so that patients can live with it—but metastasis is yet untreatable and inevitably becomes incompatible with survival. Macrophages perform a range of physiological functions and are able to activate function-specific gene repertoires; however, surface markers for selectively targeting macrophages of one or another function are still elusive, despite recent advances in the field.
“Thus, therapy attempts based on countering macrophages try to target the surface receptors that recruit them to sites of infection, inflammation or growth [5].”
DOI - https://doi.org/10.18632/oncotarget.28423
Correspondence to - Thomas T. Tapmeier - thomas.tapmeier@monash.edu
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28423
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - cancer, metastasis, macrophages, melanoma, CCR
About Oncotarget
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new editorial paper was published in Oncotarget's Volume 14 on June 12, 2023, entitled, “Are cis-spliced fusion proteins pathological in more aggressive luminal breast cancer?”
A vast majority of breast cancers (~70%) are estrogen receptor-alpha positive (ER+), for which endocrine therapy is the common treatment. However, recurrence often occurs leading to tumor progression, metastasis and eventually patient death, and the underlying molecular mechanisms remain poorly understood. In this new editorial, researchers Chia-Chia Liu and Xiao-Song Wang from the University of Pittsburgh discuss their recent study regarding recurrent gene fusions — hallmarks of some cancers that resulted either from chromosomal rearrangements or from cis- or trans-splicing.
“Importantly, selected oncogenic fusions have been matched with effective targeted therapy in several solid tumors. For instance, EML4-ALK, one of the most important oncogenic driver genes of non-small cell lung cancer (NSCLC) uncovered in recent years.”
In addition to gene fusions resulting from genomic rearrangements, a read-through SLC45A3-ELK4 fusion transcript has been identified in prostate cancer which is associated with disease progression and metastasis. Although the whole genome and RNA sequencing provide an effective way to detect fusion genes, the downstream identification and validation of fusion genes or their products in solid tumors remains a major challenge. Through analysis of RNA-seq data from TCGA, the authors of this editorial and their co-authors recently identified a neoplastic fusion transcript RAD51AP1-DYRK4 in luminal B breast cancer (~17.5%) showing higher ki67 expression which is an indication of aggressive clinical characteristics.
“In this study, we examined the utility of MEK inhibitor trametinib (Mekinist) currently used for treating melanoma with BRAF mutations, in blocking the MEK-ERK signaling driven by RAD51AP1-DYRK4 fusion. Interestingly [...] RAD51AP1-DYRK4 may endow sensitivity to MEK inhibition in luminal B breast cancer [13]. To our knowledge, this is one of the few non-traditional fusions generated by read-through events in the absence of DNA rearrangement that play an important role in tumorigenesis.”
DOI - https://doi.org/10.18632/oncotarget.28438
Correspondence to - Xiao-Song Wang - xiaosongw@pitt.edu
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28438
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - cancer, luminal B breast cancer, RAD51AP1-DYRK4, MEK inhibitor, chimerical transcript
About Oncotarget
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new editorial paper was published in Oncotarget's Volume 14 on August 10, 2023, entitled, “Inhibition of glutamine metabolism: acting on tumoral cells or on tumor microenvironment?”
Cancer cell growth and survival relies on metabolites and metabolic routes different from those used by healthy cells. Glucose and glutamine (Gln) uptake and consumption is increased by many cancer types in order to support their high growth rate. Besides being metabolized to tricarboxylic acid (TCA) cycle precursors, Gln is necessary also for the generation of nitrogen-containing metabolites, such as nucleotides, glucosamine-6-phosphate or nonessential amino acids. Indeed, nitrogen supply has been widely described as limiting for cell cycle progression.
As mitochondrial glutaminase (GLS) directs Gln into the TCA cycle, its inhibition has been suggested as a potential strategy for targeting and blocking Gln metabolism in cancer cells. In fact, GLS inhibitors block cancer cell growth in vivo and in vitro. Based on this premise, several clinical studies have been conducted to test if Gln dysregulation increases cancer patients’ survival. So far, these treatments have not been able to induce a great overall benefit for patients due to the ability of tumor cells to alter their metabolism.
Different authors have described an increase in the oxidative stress after alterations in Gln metabolism in vivo, suggesting the possibility to combine glutamine dysregulation strategies with some other therapies increasing reactive oxidative species to promote cancer cell death. In his new editorial, researcher Raul Peña from Institut Hospital del Mar d'Investigacions Mèdiques (IMIM) discusses a novel mechanism by which Gln, usually concentrated at the tumor periphery, acts as a chemoattractant for cancer-associated fibroblasts (CAFs), enhancing extracellular matrix degradation and facilitating epithelial cancer cell migration and metastasis in vivo.
“Recently, we described a new action of Gln on cancer-associated fibroblasts (CAFs) in breast cancer. [...] In our study, we determined that mesenchymal-like epithelial breast tumor cells and CAFs present a higher dependence on Gln than tumor epithelial breast cancer cells.”
DOI - https://doi.org/10.18632/oncotarget.28443
Correspondence to - Raúl Peña - rpena@imim.es
Video short - https://www.youtube.com/watch?v=HcI9CpUdbys
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28443
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - cancer, glutamine, tumor microenvironment, fibroblasts, CAF, snail1
About Oncotarget
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new review paper was published in Oncotarget's Volume 14 on August 10, 2023, entitled, “Peripheral surrogates of tumor burden to guide chemotherapeutic and immunotherapeutic strategies for HPV-associated malignancies.”
With the rapid adoption of immunotherapy into clinical practice for HPV-associated malignancies, assessing tumor burden using “liquid biopsies” would further our understanding of clinical outcomes mediated by immunotherapy and allow for tailoring of treatment based on real-time tumor dynamics.
In their new review, researchers Meghali Goswami, Jeffrey Schlom and Renee N. Donahue from the National Cancer Institute examine translational studies on peripheral surrogates of tumor burden derived from peripheral blood in HPV-associated malignancies, including levels and methylation of circulating tumor DNA (ctDNA), miRNA derived from extracellular vesicles, circulating tumor cells (CTCs), and HPV-specific antibodies and T cell responses.
“We review their utility as prognostic and predictive biomarkers of response to chemotherapy and radiation, with a focus on how they may inform and guide immunotherapies to treat locally advanced and metastatic HPV-associated malignancies. We also highlight unanswered questions that must be addressed to translate and integrate these peripheral tumor biomarkers into the clinic.”
DOI - https://doi.org/10.18632/oncotarget.28487
Correspondence to - Jeffrey Schlom - schlomj@mail.nih.gov
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28487
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - cancer, HPV-associated malignancies, immunotherapy, circulating tumor DNA, circulating tumor cells, HPV-specific antibodies
About Oncotarget
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Whole-genome doubling (WGD) and aneuploidy are two common genomic alterations that occur in human cancers. WGD is a macro-evolutionary event that results in the duplication of the entire genome, while aneuploidy is a micro-evolutionary event that results in the gain or loss of individual chromosomes or chromosome arms. Both WGD and aneuploidy can have profound effects on cellular physiology, gene expression and genome stability, and are associated with tumor initiation, progression and drug resistance.
However, the relationship between WGD and aneuploidy is complex and context-dependent. In a new editorial paper, researchers Kavya Prasad and Uri Ben-David from Tel Aviv University discuss a recent study exploring how WGD shapes the aneuploidy landscape of human cancers. Their editorial was published in Oncotarget on April 26, 2023, and entitled, “A balancing act: how whole-genome doubling and aneuploidy interact in human cancer.”
“It is known that tumors that have undergone WGD are more permissive to aneuploidy, but whether WGD also affects aneuploidy patterns has remained an open question.”
Full blog - https://www.oncotarget.org/2023/08/10/whole-genome-doubling-and-aneuploidy-in-human-cancer/
Editorial DOI - https://doi.org/10.18632/oncotarget.28374
Correspondence to - Uri Ben-David - ubendavid@tauex.tau.ac.il
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28374
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - cancer, cancer genetics, whole-genome doubling, chromosomal instability
About Oncotarget
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new research perspective was published in Oncotarget's Volume 14 on August 7, 2023, entitled, “CDK9 INHIBITORS: a promising combination partner in the treatment of hematological malignancies.”
In their new perspective, researchers Daniel Morillo, Gala Vega and Victor Moreno from Hospital Fundación Jiménez Díaz discuss Cyclin-dependent kinases (CDK) in hematological malignancies. CDKs belong to a family of serine/threonine kinases that need to form heterodimeric complexes with cyclins to perform their functions. These kinases are involved in multiple processes within cells, including cell cycle, apoptosis, transcription and differentiation. These kinases are often overexpressed in different malignancies, making them potential targets for new drugs.
Most hematological malignancies are characterized by overexpression of certain cancer promoting genes, such as MYC, MCL1 and cyclin D1. Preclinical studies in animal models have shown that CDK9 inhibitors suppress the transcription of these anti-apoptotic and pro-survival proteins, and suggest their potential synergism with other drugs. In its first in-human trial, enitociclib demonstrated clinical activity in a small cohort of patients with high grade B lymphoma with MYC and BCL2 and/or BCL6 rearrangements, inducing complete responses in 2 of 7 subjects (29%) in monotherapy.
“In summary, most hematological malignancies are characterized by overexpression of certain cancer promoting genes, such as MYC and MCL1. CDK9 inhibitors are relatively new drugs that inhibit transcription of these anti-apoptotic and pro-survival proteins.”
DOI - https://doi.org/10.18632/oncotarget.28473
Correspondence to - Victor Moreno - victor.moreno@startmadrid.com
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28473
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - cancer, cyclin-dependent kinases (CDK), CDK9, hematological malignancies
About Oncotarget
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new editorial paper was published in Oncotarget's Volume 14 on May 4, 2023, entitled, “AGO2 in T-prolymphocytic leukemia: its canonical and noncanonical deregulation and function.”
In their new editorial, researchers Till Braun, Hanna Klepzig and Marco Herling from University of Cologne and University of Leipzig T-prolymphocytic leukemia (T-PLL) — a mature T-cell neoplasm with an aggressive and treatment refractory course.
“In light of limited therapeutic options median overall survival times from diagnosis is hardly longer than 2 years.”
There is currently no FDA- or EMA-approved drug for the treatment of T-PLL. Although 80–90% of patients experience a response to the most efficient single agent Alemtuzumab, relapses are common within the first 12–24 months following this first-line treatment. One of the defining characteristics of T-PLL is the presence of the chromosomal aberrations inv(14) or t(14;14), which lead to constitutive expression of the proto-oncogene T-cell leukemia 1A (TCL1A).
This adapter molecule is centrally implicated in the enhanced T-cell receptor (TCR) signaling that is observed in the memorytype malignant T-cell. Other recurrent genomic alterations that have been identified in T-PLL affect the genes ataxia telangiectasia mutated (ATM), Janus kinase (JAK), signal transducer and activator of transcription (STAT), and MYC. In a recent study published by Braun et al., the team made significant advances in the understanding of the biology of T-PLL at the level of post-transcriptional gene regulation.
“For the first time, descriptive and mechanistic data implicated the involvement of molecules of the RNA interference (RNAi) machinery in T-PLL’s leukemogenesis and by that refined our current disease model by concepts beyond protein-coding genes.”
DOI - https://doi.org/10.18632/oncotarget.28378
Correspondence to - Marco Herling - marco.herling@medizin.uni-leipzig.de
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28378
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - cancer, leukemia, T-PLL, AGO2, microRNA
About Oncotarget
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new editorial paper was published in Oncotarget's Volume 14 on May 12, 2023, entitled, “Targeting H3K27me3 loss in pediatric brain tumors - a perspective on epigenetically guided cancer therapy.”
High-grade tumors of the central nervous system, including medulloblastoma, ependymoma and DMG (diffuse midline glioma, formerly known as DIPG (diffuse intrinsic pontine glioma)), constitute a major challenge in pediatric oncology. They are characterized by an aggressive growth and high relapse rates and claim the lives of many pediatric cancer patients.
Both medulloblastoma and ependymoma are treated with surgical resection followed by adjuvant radiation therapy. DMG, on the other hand, diffusely infiltrates the brain stem making a resection virtually impossible. Thus, radiotherapy is the primary treatment modality for this tumor. While radiation temporarily attenuates the progression of DMG this brain cancer remains incurable and most children succumb to their disease.
In his new editorial, Dr. Michael Goldstein from Johns Hopkins University School of Medicine discusses the extensively investigated molecular profiles of the aforementioned pediatric brain tumors demonstrating distinct epigenetic traits.
“Strikingly, a global loss of H3K27 tri-methylation (H3K27me3) as a result of the dominant-negative histone H3K27M mutation was found to be a hallmark of DMG occurring in the majority of the tumors.”
H3K27me3 is a product of the EZH2 histone methyltransferase affecting multiple cellular processes including transcription, chromatin structure and DNA damage response. Similarly, the aggressive PFA ependymoma subgroup is characterized by a lack of H3K27me3 due to an overexpression of the EZHIP protein that acts as an EZH2 inhibitor whereas less aggressive PFB tumors retain normal H3K27me3 levels. However, no comprehensive analysis of H3K27me3 expression patterns in medulloblastoma has been performed and the significance of this epigenetic mark in pediatric brain tumors has remained unknown.
“To address this, we have investigated the levels of the H3K27me3 histone mark and its role in treatment response of non-WNT/SHH medulloblastoma comprising group 3 and group 4 tumors. We demonstrated that about 50% of the tumors in patients with group 3 and group 4 medulloblastoma are H3K27me3 deficient. Strikingly, loss of H3K27me3 was associated with high relapse rates and poor survival.”
DOI - https://doi.org/10.18632/oncotarget.28427
Correspondence to - Michael Goldstein - mgolds33@jhu.edu
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28427
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - cancer, epigenetics, brain tumor, EZH2, H3K27me3, radiation therapy
About Oncotarget
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new editorial paper was published in Oncotarget's Volume 14 on July 20, 2023, entitled, “Multiclonality of ER expression in DCIS – Implications for clinical practice and future research.”
Estrogen receptor (ER) expression is not routinely evaluated in ductal carcinoma in situ (DCIS). This may be because the prognostic role of ER in DCIS was unclear until the UK/ ANZ DCIS trial in 2021 showed that lack of ER expression in DCIS was associated with a greater than 3-fold risk of ipsilateral recurrence. This was the largest (to date) case-control study nested in a DCIS randomized trial.
The meticulous study design eliminated treatment allocation bias as well as treatment-related confounding. This was also the first-ever study to show that ER expression in DCIS is multi-clonal — having very important clinical and research implications. A small proportion of otherwise ER-positive DCIS also contained carcinoma in situ (CIS) duct/s that completely lacked ER expression.
“This admixture of clearly ER-positive and ER-negative ducts is not the same as heterogeneity in ER expression and I labeled such DCIS cases as multiclonal DCIS even if just one CIS duct in the entire section lacked ER expression.”
In his new editorial, Dr. Mangesh A. Thorat from Guy's and St Thomas' NHS Foundation Trust, Queen Mary University of London and King's College London discusses this study in greater detail, the clinical implications of ER status in DCIS, the potential for avoiding overtreatment and undertreatment based on ER expression, and the importance of simple clinical observations in research.
“In summary, ER is a strong and independent prognostic biomarker in DCIS and our novel clonal method is a more accurate method to assess ER status in DCIS.”
DOI - https://doi.org/10.18632/oncotarget.28450
Correspondence to - Mangesh A. Thorat - thoratmangesh@gmail.com; m.thorat@qmul.ac.uk
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28450
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - cancer, ductal carcinoma in situ (DCIS), invasive breast cancer, ER, recurrence, clonality
About Oncotarget
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
The strong correlation between obesity and a myriad of life-limiting diseases and conditions, including type 2 diabetes, is widely recognized and acknowledged in the research community. A less defined correlation is that between obesity, diabetes and lung cancer. Whether this association is directly causal or if there are underlying contributing factors is not yet clear.
“Although obesity and type 2 diabetes mellitus (T2DM) have been associated with lung cancer (LC) development, several confounding factors, such as chronic inflammation, high insulin levels, microbiome, as well as the oncogenic potential of growth and sexual hormones, have introduced uncertainty and avoid the fully recognition of this relationship [1, 2].”
Given the existence of this association, scientists are testing therapeutic regimens that may have the potential to fight all three issues — together. Metformin, a drug commonly prescribed to treat type 2 diabetes, helps lower blood sugar levels by improving insulin sensitivity and reducing glucose production in the liver. The metabolic-modifying properties of metformin aid in treating diabetes and obesity. Metformin has also garnered attention for its potential anti-aging properties and may hold promise for treating age-related diseases, including cancer. Lately, there has been growing interest in testing metformin in combination therapies to combat cancer-promoting conditions induced by obesity.
The "Obesity Paradox"
While the link between morbidity and obesity may seem cut-and-dry, researchers have discovered a surprising trend. The "obesity paradox" suggests that, in certain instances, individuals classified as overweight or mildly obese seem to fare better or have a survival advantage compared to those with normal weight or even underweight counterparts. This paradox has been particularly observed in certain chronic illnesses, such as heart failure, chronic kidney disease, and even in the context of aging. Researchers are still striving to understand the underlying mechanisms driving this phenomenon.
In a new editorial, researchers Pedro Barrios-Bernal, Norma Hernández-Pedro, Luis Lara-Mejía, and Oscar Arrieta from Instituto Nacional de Cancerología in Mexico City discuss the obesity paradox and its potential therapeutic opportunities in the context of lung cancer. Their editorial paper was published in Oncotarget on July 1, 2023, and entitled, “Obesity paradox and lung cancer, metformin-based therapeutic opportunity?” They suggest that metformin may have potential therapeutic effects for both obesity and lung cancer. The researchers explore the mechanisms by which metformin may modify tumor metastatic properties and promote an antitumor immune response. They also discuss the potential implications of the obesity paradox in the context of lung cancer treatment and the potential benefits of metformin use in combination with antineoplastic therapies.
In a 2019 study, the researchers conducted a phase 2 randomized clinical trial investigating the effect of metformin combined with tyrosine kinase inhibitors (TKIs) (compared to TKIs alone) in patients with epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma. They found that the addition of metformin to standard EGFR-TKI therapy in patients with advanced lung adenocarcinoma significantly improved progression-free survival. In their 2022 study, the researchers performed a secondary analysis of the same study, now measuring the association of body mass index (BMI). This time, they reported that the survival outcome in patients with EGFR-mutated lung adenocarcinoma was greater with patients with a BMI higher than 24. The findings suggest that this treatment combination has a selective effect in obese populations and a lack of benefit in patients with a BMI less than 24, thus contributing to the obesity paradox. [...]
BUFFALO, NY- July 26, 2023 – A new research paper was published in Oncotarget's Volume 14 on July 20, 2023, entitled, “The uncharacterized transcript KIAA0930 confers a cachexic phenotype on cancer cells.”
Patients with cancer cachexia have a poor prognosis and impaired quality of life. Numerous studies using preclinical models have shown that inflammatory cytokines play an important role in the development of cancer cachexia; however, no clinical trial targeting cytokines has been successful. Therefore, it is essential to identify molecular mechanisms to develop anti-cachexia therapies.
In this new study, researchers Takahiro Yamakawa, Guoxiang Zhang, Liza Bengrine Najjar, Chun Li, and Keiichi Itakura from the Beckman Research Institute of City of Hope identified the uncharacterized transcript KIAA0930 as a candidate cachexic factor based on analyses of microarray datasets and an in vitro muscle atrophy assay.
“We here report the initial characterization of KIAA0930.”
While conditioned media from pancreatic, colorectal, gastric, and tongue cancer cells caused muscle atrophy in vitro, conditioned medium from KIAA0930 knockdown cells did not. The PANC-1 orthotopic xenograft study showed that the tibialis anterior muscle weight and cross-sectional area were increased in mice bearing KIAA0930 knockdown cells compared to control mice. Interestingly, KIAA0930 knockdown did not cause consistent changes in the secretion of inflammatory cytokines/chemokines from a variety of cancer cell lines. An initial characterization experiment showed that KIAA0930 is localized in the cytosol and not secreted from cells.
“These data suggest that the action of KIAA0930 is independent of the expression of cytokines/chemokines and that KIAA0930 could be a novel therapeutic target for cachexia.”
Read the full study: DOI: https://doi.org/10.18632/oncotarget.28476
Correspondence to: Takahiro Yamakawa
Email: tyamakawa@coh.org
Keywords: KIAA0930, cancer cachexia, muscle atrophy, inflammatory cytokines/chemokines, protein secretion
About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter Facebook YouTube Instagram LinkedIn Pinterest LabTube Soundcloud
Sign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28476
For media inquiries, please contact: media@impactjournals.com.
BUFFALO, NY- July 24, 2023 – A new research paper was published in Oncotarget's Volume 14 on July 20, 2023, entitled, “Development of a multiplex assay to assess activated p300/CBP in circulating prostate tumor cells.”
Reduced SIRT2 deacetylation and increased p300 acetylation activity leads to a concerted mechanism of hyperacetylation at specific histone lysine sites (H3K9, H3K14, and H3K18) in castration-resistant prostate cancer (CRPC). In this new study, researchers Mikolaj Filon, Bing Yang, Tanaya A. Purohit, Jennifer Schehr, Anupama Singh, Marcelo Bigarella, Peter Lewis, John Denu, Joshua Lang, and David F. Jarrard from the University of Wisconsin examined whether circulating tumor cells (CTCs) identify patients with altered p300/CBP acetylation.
“In the current study, employing a novel Exclusion-based Sample Preparation (ESP) technology (9) (Supplementary Figure 1) to isolate CTCs, we evaluated p300 activity, SIRT2 expression and H3K18 acetylation in CTCs in a series of patients with sensitivity or resistance to ADT.”
CTCs were isolated from 13 advanced PC patients using Exclusion-based Sample Preparation (ESP) technology. Bound cells underwent immunofluorescent staining for histone modifying enzymes (HMEs) of interest and image capture with NIS-Elements software. Using the cBioPortal PCF/SU2C dataset, the response of CRPC to androgen receptor signaling inhibitors (ARSI) was analyzed in 50 subjects.
Staining optimization and specificity revealed clear expression of acetyl-p300, acetyl-H3K18, and SIRT2 on CTCs (CK positive, CD45 negative cells). Exposure to A-485, a selective p300/CBP catalytic inhibitor, reduced p300 and H3K18 acetylation. In CRPC patients, a-p300 strongly correlated with its target acetylated H3k18 (Pearson’s R = 0.61), and SIRT2 expression showed robust negative correlation with a-H3k18 (R = −0.60).
A subgroup of CRPC patients (6/11; 55%) demonstrated consistent upregulation of acetylation based on these markers. To examine the clinical impact of upregulation of the CBP/p300 axis, CRPC patients with reduced deacetylase SIRT2 expression demonstrate shorter response times to ARSI therapy (5.9 vs. 12 mo; p = 0.03). A subset of CRPC patients demonstrate increased p300/CBP activity based on a novel CTC biomarker assay.
“With further development, this biomarker suite may be used to identify candidates for CBP/p300 acetylation inhibitors in clinical development.”
Read the full study: DOI: https://doi.org/10.18632/oncotarget.28477
Correspondence to: David F. Jarrard
Email: jarrard@urology.wisc.edu
Keywords: prostate cancer, circulating tumor cells, p300/CBP
About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter Facebook YouTube Instagram LinkedIn Pinterest LabTube Soundcloud
Sign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28477
Click here to subscribe to Oncotarget publication updates.
For media inquiries, please contact: media@impactjournals.com.
A new editorial paper was published in Oncotarget's Volume 14 on May 26, 2023, entitled, “Combined targeting of HEDGEHOG signaling and BRD4 as a novel therapeutic option against melanoma.”
The Hedgehog-GLI (HH/GLI) pathway is aberrantly activated in several types of cancer. Canonical HH/ GLI pathway is triggered by binding of HH ligands to the twelve-pass transmembrane receptor Patched 1 (PTCH1), which retrieves its inhibition on the seven-pass transmembrane G protein-coupled receptor Smoothened (SMO), leading to the activation of the GLI transcription factors. Small molecules inhibitors targeting the essential pathway transducer SMO (e.g., vismodegib, sonidegib) have demonstrated therapeutic efficacy in HH-dependent tumors, such as basal cell carcinoma (BCC) and medulloblastoma (MB).
However, the therapeutic efficacy of these SMO antagonists is limited by the development of acquired resistance and recurrence after drug withdrawal, and by additional oncogenic signals responsible for noncanonical activation of GLI transcription factors [1]. In this new editorial, researchers Silvia Pietrobono and Barbara Stecca from the University of Verona and the Institute for Cancer Research and Prevention (CRL-ISPRO) state that they subscribe to the idea that targeting non-canonical HH/GLI signaling will improve the response rate and durability of therapeutic effects exerted by SMO inhibition. Therefore, they propose that the identification of novel targetable regulators that function downstream of SMO, especially those acting at the transcriptional level, is of critical importance to effectively inhibit the HH pathway and prevent tumor relapse.
“Collectively, the findings presented by Pietrobono et al. pave the path for the development of a novel therapeutic strategy in tumors having both canonical and non-canonical HH/GLI signaling activation, such as melanoma.”
DOI - https://doi.org/10.18632/oncotarget.28441
Correspondence to - Silvia Pietrobono - silvia.pietrobono@univr.it, and Barbara Stecca - b.stecca@ispro.toscana.it
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28441
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - cancer, melanoma, hedgehog signaling, BRD4, SOX2, GLI1
About Oncotarget
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new case report was published in Oncotarget's Volume 14 on July 7, 2023, entitled, “Intrathoracic synovial sarcoma with BRAF V600E mutation.”
Synovial sarcoma (SS) is a highly malignant mesenchymal tumor that occurs mainly in adolescents and young adults. The treatment of SS is multimodal, involving surgery, radiotherapy and chemotherapy. The overall prognosis is generally quite satisfactory in children and adolescents with localized SS at diagnosis. However, the outcome remains poor for patients who relapse, with a reported 5-year post-relapse survival of around 30%.
In this new paper, researchers Ida Russo, Sabina Barresi, Pier Luigi Di Paolo, Valentina Di Ruscio, Giada Del Baldo, Annalisa Serra, Silvia Vallese, Evelina Miele, Angela Mastronuzzi, Rita Alaggio, Andrea Ferrari, and Giuseppe Maria Milano from Italy’s Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) report the case of a 15-year-old boy with intrathoracic synovial sarcoma who relapsed after standard chemotherapy, surgery and radiotherapy. The molecular analysis of the tumor identified a BRAF V600E mutation at time of progression of relapsed disease under third line systemic treatment.
This mutation is commonly seen in melanomas and papillary thyroid cancers, but less prevalent (typically <5%) across a variety of other cancer types. The patient underwent selective BRAF inhibitor Vemurafenib treatment achieving partial response (PR) with a progression free survival (PFS) ratio of 1.6 months and an overall survival of 19 months, alive in continuous PR. This case highlights the role of routine next generation sequencing (NGS) used to drive treatment choice and to investigate SS tumors for BRAF mutations.
“Our data highlight the importance of implementing molecular tests in SS patients to evaluate BRAF mutational actual incidence in these neoplasms.”
DOI - https://doi.org/10.18632/oncotarget.28475
Correspondence to - Giuseppe Maria Milano - giuseppemaria.milano@opbg.net
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28475
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - synovial sarcoma, next-generation sequencing, BRAF V600E mutation, targeted therapy
About Oncotarget
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Ras plays a crucial role in controlling various cellular processes by switching between active (Ras-GTP) and inactive (Ras-GDP) states with the help of specific molecules. In its active form, Ras interacts with multiple effector proteins, initiating downstream events. Humans have three Ras genes, resulting in four isoforms that have distinct expression patterns and unique functions in different tissues. Posttranslational modifications target Ras to the cell membrane, where it can form dimers and interact with effectors through common domains. Ras mutations, commonly found in pancreatic, colorectal and lung cancers, lock Ras in an active state, promoting continuous cell division and proliferation. Ras signaling disruption occurs through reduced catalytic activity, altered effector binding and decreased affinity for other regulatory proteins.
Although Ras has been considered difficult to target, recent advancements have identified potential binding pockets that can be addressed by small molecules, peptidomimetics and proteins. Inhibitors designed to covalently bind to the Ras G12C mutant have shown promise, leading to FDA-approved drugs for specific lung cancers. Additionally, protein-based inhibitors that target Ras and its interactions with effectors, regulatory proteins and guanine nucleotide exchange factors offer alternative strategies for therapeutic intervention. These developments have challenged the notion that Ras is “undruggable” and highlight the potential for effective treatments against various cancer types.
On July 1, 2023, researchers Atilio Tomazini and Julia M. Shifman from The Hebrew University of Jerusalem published a new review paper in Oncotarget, entitled, “Targeting Ras with protein engineering.” The authors provide an overview of the challenges associated with targeting Ras proteins with small molecules and discuss how protein engineering has emerged as a promising method to overcome these challenges.
“While the development of small-molecule Ras inhibitors has been reviewed elsewhere [40], we focus our review on protein-based Ras inhibitors, describing the methods for their engineering, various scaffolds used for inhibitor design, and prospects for delivery of the designed Ras inhibitors into the cellular cytoplasm, where Ras is located.”
Full blog - https://www.oncotarget.org/2023/07/14/targeting-ras-in-cancer-therapies-advances-in-protein-engineering/
Paper DOI - https://doi.org/10.18632/oncotarget.28469
Correspondence to - Julia M. Shifman - jshifman@mail.huji.ac.il
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28469
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - Ras oncogene, anti-Ras therapeutics, Ras targeting, protein engineering, protein design
About Oncotarget
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new research paper was published in Oncotarget's Volume 14 on July 7, 2023, entitled, “Effectiveness and toxicity of cetuximab with concurrent RT in locally advanced cutaneous squamous cell skin cancer: a case series.”
Treatment for locally advanced cutaneous squamous cell cancers (laCSCC) remains poorly defined. Most laCSCC tumors express high levels of epidermal growth factor receptors (EGFR). Cetuximab has activity in other EGFR expressing cancers and enhances the effectiveness of radiotherapy.
In this new study, researchers Mark Chang, Wolfram Samlowski and Raul Meoz from University Medical Center of Southern Nevada, Comprehensive Cancer Centers of Nevada, University of Nevada Las Vegas, and University of Nevada Reno conducted a retrospective review of institutional data and identified 18 patients with laCSCC treated with cetuximab induction and concurrent radiotherapy.
“We performed a retrospectively review of treatment outcome and toxicity in our patients who received concurrent cetuximab and radiotherapy to show an additional potentially effective treatment option for patients with laCSCC. The goal is also to provide data to inform the design of potential prospective clinical trials.”
The loading dose of cetuximab was 400 mg/m² IV. Subsequent weekly doses of 250 mg/m² IV were infused throughout the period of radiation. The treatment doses ranged from 4500–7000 cGy, with a dose fraction of 200-250 cGy. The objective response rate was 83.2% with 55.5% complete responses and 27.7% partial responses.
Median progression-free survival was 21.6 months. Progression-free survival was 61% at 1 year and 40% at 2 years. With longer follow-up, some patients developed a local recurrence (16.7%), distant metastases (11.1%) or a second primary cancer (16.3%). Cetuximab was well tolerated, with 68.4% patients experienced only mild acneiform skin rash or fatigue (Grade 1 or 2). Radiotherapy produced expected side effects (skin erythema, moist desquamation, mucositis).
“Cetuximab plus radiotherapy represents an active and tolerable treatment option for laCSCC, including patients with contraindications for checkpoint inhibitor therapy.”
DOI - https://doi.org/10.18632/oncotarget.28470
Correspondence to - Wolfram Samlowski - wsamlowski1@gmail.com
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28470
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - keratinocyte carcinoma, squamous cell skin cancer, cetuximab, epidermal growth factor receptor, radiation therapy
About Oncotarget:
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
For media inquiries, please contact: media@impactjournals.com.
A new research perspective was published in Oncotarget's Volume 14 on July 1, 2023, entitled, “Deciphering the mechanisms of action of progesterone in breast cancer.”
A practice-changing, randomized, controlled clinical study established that preoperative hydroxyprogesterone administration improves disease-free and overall survival in patients with node-positive breast cancer. In this new perspective, researchers Gaurav Chakravorty, Suhail Ahmad, Mukul S. Godbole, Sudeep Gupta, Rajendra A. Badwe, and Amit Dutt from Tata Memorial Centre, Homi Bhabha National Institute and MIT World Peace University summarized evidence from their studies that preoperative hydroxyprogesterone administration may improve disease-free and overall survival in patients with node-positive breast cancer by modulating cellular stress response and negative regulation of inflammation.
“This research perspective is aimed to highlight the multipronged roles of progesterone in breast cancer that underlie the associated clinical response. We also present our opinion on the role of progesterone in overcoming endocrine resistance in the patients, especially by countering the genomic effects of overexpression and mutation of ESR1 and its targets.”
Non-coding RNAs, particularly DSCAM-AS1, play a regulatory role in this process, along with the upregulation of the kinase gene SGK1 and activation of the SGK1/AP-1/NDRG1 axis. Progesterone-induced modification of the progesterone receptor and estrogen receptor genomic binding pattern is also involved in orchestrating estrogen signaling in breast cancer, preventing cell migration and invasion, and improving patient outcomes. The team continues on to highlight the role of progesterone in endocrine therapy resistance, which could lead to novel treatment options for patients with hormone receptor-positive breast cancer and for those who develop resistance to traditional endocrine therapies.
“Overall, while preoperative hydroxyprogesterone administration appears to be a promising strategy for improving the prognosis of patients with node-positive breast cancer, the investigation of the mechanism of actions of progesterone in breast cancer remains an important area of research that holds great promise for improving patient outcomes.”
DOI - https://doi.org/10.18632/oncotarget.28455
Correspondence to - Amit Dutt - adutt@actrec.gov.in
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28455
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - breast cancer, progesterone, DSCAM-AS1, endocrine therapy
About Oncotarget
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new research paper was published in Oncotarget's Volume 14 on July 1, 2023, entitled, “Transformation of immunosuppressive mtKRAS tumors into immunostimulatory tumors by Nerofe and Doxorubicin.”
Members of the rat sarcoma viral oncogene (RAS) subfamily KRAS are frequently mutated oncogenes in human cancers and have been identified in pancreatic ductal, colorectal, and lung adenocarcinomas. Recently, two drugs that specifically target KRAS G12C, sotorasib (Lumakras™) and adagrasib (Krazati™), have received accelerated approval by the FDA for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, who have received at least one prior systemic therapy. These drugs are the first RAS GTPase family inhibitors to be approved for clinical use, representing a major breakthrough in the field of precision oncology.
In this new study, researchers Joel Ohana, Uziel Sandler, Orly Devary, and Yoram Devary from Immune System Key (ISK) and Jerusalem College of Technology show that a derivative of the hormone peptide Tumor Cell Apoptosis Factor (TCApF), Nerofe™ (dTCApFs), in combination with Doxorubicin (DOX) substantially reduces viability of tumor cells.
“The objective of the present study was to investigate the synergistic effect of the combination of Nerofe and DOX in colorectal cancer and its underlying mechanism.”
It was observed that the combination of Nerofe and DOX downregulated KRAS signaling via miR217 upregulation, resulting in enhanced apoptosis of tumor cells. In addition, the combination of Nerofe and DOX also resulted in activation of the immune system against tumor cells, manifested by an increase in the immunostimulatory cytokines IL-2 and IFN-γ as well as the recruitment of NK cells and M1 macrophages to the tumor site.
“In conclusion, we demonstrated that the combination of Nerofe and DOX exerts a synergistic effect during mCRC treatment, which could stem from several independent and complementary mechanisms of action.”
DOI - https://doi.org/10.18632/oncotarget.28467
Correspondence to - Yoram Devary - ydevary@immunesk.com
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28467
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - Colorectal cancer, KRAS, apoptosis, hormone peptide, endoplasmic reticulum stress
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new editorial paper was published in Oncotarget's Volume 14 on June 12, 2023, entitled, “ERβ as a mediator of estrogen signaling in inflammatory breast cancer.”
In this new editorial, researchers Harika Nagandla and Christoforos Thomas from Houston Methodist Neal Cancer Center discuss inflammatory breast cancer (IBC)—a rare and aggressive form of breast cancer which accounts for 2–4% of all new breast cancer cases detected in the United States. Even with the application of standard multi-modality treatment approach that incorporates neoadjuvant chemotherapy, radiation and surgery, the 5-year survival rate for IBC is only about 40–50%. Breast cancer can be typically stratified into different types based on the presence of molecular drivers such estrogen receptor (ERα), progesterone receptor (PR) or human epidermal growth factor receptor 2 (HER2), which inform the treatment choice.
For IBC, there is a substantially higher incidence of ERα negativity compared with other forms of breast cancer that can reach up to 60%. A specific targetable driver signaling pathway has not been identified so far. About one in three patients already have distant metastasis at the time of diagnosis, contributing to the aggressiveness and poor outcomes associated with IBC.
Despite the absence of ERα from the majority of IBC tumors, estrogen signaling has been implicated in progression of the disease through ERα-independent pathways. ERβ is a ligand activated transcription factor that mediates effects of estrogen, along with ERα in different tissues during growth and development by regulating transcription of target genes. Tumor suppressive effects of ERβ have been documented in diverse cancer types such as thyroid, kidney, prostate, glioblastoma, ovarian and breast cancer.
“The work from our group [6] establishes ERβ as a tumor suppressor in IBC by demonstrating its strong antimetastatic activity in preclinical models of the disease and delineating the mechanism of action.”
DOI - https://doi.org/10.18632/oncotarget.28425
Correspondence to - Christoforos Thomas - cthomas3@houstonmethodist.org
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28425
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - inflammatory breast cancer, IBC, ERβ, metastasis, actin based cell migration
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
On the bright side, polo-like kinase 1 (PLK1) is considered a master regulator of the ever-important cell cycle. On the dark side, PLK1 expression (at both the mRNA and protein level) has shown to be upregulated in tumor cells, suggesting that PLK1 may also contribute to tumorigenesis. Despite this direct association, researchers studying the role of PLK1 in cancer have encountered a problem: a lack of appropriate animal models for experimentation.
“Even though studies have suggested that PLK1 contributes to tumorigenesis, the ability of PLK1 to drive oncogenic transformation on its own in vivo was still questionable due to a lack of sophisticated animal models for experimentation [18, 19].”
This problem may have been solved in 2021. In a new editorial paper, researchers Lilia Gheghiani and Zheng Fu from Virginia Commonwealth University discuss a recent study using their team’s new genetically engineered mouse (GEM) model to assess the ability of PLK1 to be a sole driver of oncogenic transformation in vivo. Their editorial was published in Oncotarget’s Volume 14 on June 27, 2023, and entitled, “The dark side of PLK1: Implications for cancer and genomic instability.”
Full blog - https://www.oncotarget.org/2023/06/29/novel-gem-model-unveils-plk1s-role-in-tumorigenesis/
Paper DOI - https://doi.org/10.18632/oncotarget.28456
Correspondence to - Zheng Fu - zheng.fu@vcuhealth.org
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28456
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - cancer, polo-like kinase 1 (PLK1), oncogene, chromosomal instability, cell cycle checkpoints, tumorigenesis
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new editorial paper was published in Oncotarget's Volume 14 on June 21, 2023, entitled, “Decoding the mechanism behind MCL-1 inhibitors: A pathway to understanding MCL-1 protein stability.”
The successful development of the BCL-2 inhibitor venetoclax, currently approved for chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML), encouraged the development of inhibitors that target other antiapoptotic proteins, particularly Myeloid Leukemia 1 (MCL-1). MCL-1 is among the top genes amplified in several cancers and is implicated in cancer progression, drug resistance and poor prognosis. It protects cancer cells from apoptosis and decreases their sensitivity to targeted agents or chemotherapeutics.
In this new editorial, researchers Shady I. Tantawy, Natalia Timofeeva, Ana Hernandez, Aloke Sarkar and Varsha Gandhi from The University of Texas MD Anderson Cancer Center discussed their recent investigation into the mechanism of MCL-1 inhibitor (MCL-1i)-induced Mcl-1 protein stability. The team explored underlying molecular mechanisms that contribute to MCL-1i-induced MCL-1 protein accumulation and its implications. Their study revealed a complex and multifaceted nature of MCL-1 protein accumulation in B-cell malignancies upon treatment with MCL-1i (AMG-176 and AZD5991).
“Collectively, these findings may have important implications for the development of next-generation MCL-1i with improved efficacy and safety profiles.”
DOI - https://doi.org/10.18632/oncotarget.28440
Correspondence to - Aloke Sarkar - asarkar@mdanderson.org, and Varsha Gandhi - vgandhi@mdanderson.org
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28440
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - AMG-176, AZD5991, B-cell leukemia, MCL-1 inhibitor, MCL-1 protein
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new research paper was published in Oncotarget's Volume 14 on June 21, 2023, entitled, “Diphenyl ditelluride anticancer activity and DNA topoisomerase I poisoning in human colon cancer HCT116 cells.”
Diphenyl ditelluride (DPDT) is an organotellurium (OT) compound with pharmacological properties, including antioxidant, antigenotoxic and antimutagenic activities when applied at low concentrations. However, DPDT as well as other OT compounds also show cytotoxicity against mammalian cells when treatments occur at higher drug concentrations. The underlying mechanisms of toxicity of DPDT against tumor cells have previously been poorly explored.
In this new study, researchers André Luiz Mendes Juchem, Cristiano Trindade, Juliana Bondan da Silva, Miriana da Silva Machado, Temenouga Nikolova Guecheva, Jaqueline Cesar Rocha, Jenifer Saffi, Iuri Marques de Oliveira, João Antonio Pêgas Henriques, and Alexandre Escargueil from the Federal University of Rio Grande do Sul, Sorbonne Université, Federal University of Health Sciences of Porto Alegre, Lutheran University of Brazil, Bulgarian Academy of Sciences, and University of Vale do Taquari aimed to investigate the effects of DPDT against both human cancer and non-tumorigenic cells.
“Together, our results will help to better define DPDT as a potential drug candidate for treating CRC [colorectal cancer].”
The researchers used the colonic HCT116 cancer cells and the MRC5 fibroblasts as models. Their results showed that DPDT preferentially targets HCT116 cancer cells when compared to MRC5 cells with IC50 values of 2.4 and 10.1 μM, respectively. This effect was accompanied by the induction of apoptosis and a pronounced G2/M cell cycle arrest in HCT116 cells.
Furthermore, DPDT induces DNA strand breaks at concentrations below 5 μM in HCT116 cells and promotes the occurrence of DNA double strand breaks mostly during S-phase as measured by γ-H2AX/EdU double staining. Finally, DPDT forms covalent complexes with DNA topoisomerase I, as observed by the TARDIS assay, with a more prominent effect observed in HCT116 than in MRC5 cells. Taken together, the results of this study show that DPDT preferentially targets HCT116 colon cancer cells likely through DNA topoisomerase I poisoning.
“This makes DPDT an interesting molecule for further development as an anti-proliferative compound in the context of cancer.”
Read the full paper: DOI: https://doi.org/10.18632/oncotarget.28465
Correspondence to: João Antonio Pêgas Henriques, Alexandre Escargueil
Email: pegas.henriques@ufrgs.br, alexandre.escargueil@gmail.com
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28465
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - colorectal cancer, HCT116, diphenyl ditelluride, organotellurium, topoisomerase I
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new research perspective was published in Oncotarget's Volume 14 on June 19, 2023, entitled, “Targeting GITR in cancer immunotherapy – there is no perfect knowledge.”
In this new perspective, researchers Diwakar Davar and Roberta Zappasodi from the University of Pittsburgh Medical Center (UPMC), University of Pittsburgh, Weill Cornell Medical College, and Weill Cornell Graduate School of Medical Sciences discuss the glucocorticoid-induced TNFR-related protein (GITR), belonging to the TNFR superfamily (TNFRSF) and stimulating both the acquired and innate immunity. GITR is broadly expressed on immune cells, particularly regulatory T cells (Tregs) and natural killer (NK) cells.
“Given its potential to promote T effector function and impede Treg immune suppression, GITR is an attractive target for cancer immunotherapy.”
Preclinically, GITR agonists have demonstrated potent anti-tumor efficacy singly and in combination with a variety of agents, including PD-1 blockade. Multiple GITR agonists have been advanced into the clinic, although the experience with these agents has been disappointing. Recent mechanistic insights into the roles of antibody structure, valency, and Fc functionality in mediating anti-tumor efficacy may explain some of the apparent inconsistency or discordance between preclinical data and observed clinical efficacy.
Overall, the clinical results obtained so far with GITR agonist agents have demonstrated specific immune effects in the expected immune cell populations based on preclinical studies. However, these effects have not produced substantial therapeutic activity in human cancer patients. A maturing understanding of the immune responses to GITR agonism in human cancer has clarified novel issues specific to drug development in this space including Ab structure (monospecific and bispecific mAbs and co-stimulatory GITR ligands), Ab valency, and Fc functionality.
“This improved understanding of the immune responses to GITR agonism in patients should be kept in consideration for the design of novel rational combinations or treatment regimens in earlier disease settings where immunotherapy is gradually becoming the treatment of choice.”
DOI - https://doi.org/10.18632/oncotarget.28461
Correspondence to - Diwakar Davar - davard@upmc.edu
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28461
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - cancer, immunotherapy, programmed death-1 (PD-1), cytotoxic T-lymphocyte Antigen-4 (CTLA-4), glucocorticoid-induced TNFR-related protein (GITR)
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new research paper was published in Oncotarget's Volume 14 on June 19, 2023, entitled, “Utilizing metformin to prevent metabolic syndrome due to androgen deprivation therapy (ADT): a randomized phase II study of metformin in non-diabetic men initiating ADT for advanced prostate cancer.”
Androgen deprivation therapy (ADT) can lead to metabolic syndrome (MS) and is implicated in ADT-resistance. Metformin showed antineoplastic activity through mTOR inhibition secondary AMPK-activation.
To investigate whether metformin mitigated ADT-related MS, researchers Devalingam Mahalingam, Salih Hanni, Anthony V. Serritella, Christos Fountzilas, Joel Michalek, Brian Hernandez, John Sarantopoulos, Paromitta Datta, Ofelia Romero, Sureshkumar Mulampurath Achutan Pillai, John Kuhn, Michael Pollak6, and Ian M. Thompson from the University of Texas Health Science Center, Robert H Lurie Comprehensive Cancer Center of Northwestern University, Roswell Park Cancer Institute, Mays Cancer Center at University of Texas Health, Audie Murphy VA Hospital, McGill University, and Christus Health conducted a randomized double-blind phase II trial of metformin 500 mg TID or placebo in non-diabetic patients with biochemically-relapsed or advanced prostate cancer (PC) due for ADT.
“To test these hypotheses, we conducted a phase II randomized, placebo-controlled, prospective study of metformin vs. placebo in patients with advanced, castrate sensitive PC treated with ADT (NCT:01620593).”
Fasting serum glucose, insulin, PSA, metformin, weight, and waist circumference (WC) were measured at baseline, week 12 and 28. The primary endpoint was a group of MS metrics. Secondary endpoints include PSA response, safety, serum metformin concentrations and analysis of downstream an mTOR target, phospho-S6-kinase.
Thirty-six men were randomized to either metformin or placebo. Mean age was 68.4. Mean weight, WC and insulin levels increased in both arms. At week 12 and 28, no statistical differences in weight, WC or insulin were observed in either arm. No significant difference in percentage of patients with PSA <0.2 at week 28 between metformin (45.5%) vs. placebo (46.7%). Analysis in the metformin-arm showed variable down-regulation of phospho-S6 kinase.
“In our small study, metformin added to ADT did not show a reduced risk of ADT-related MS or differences in PSA response.”
DOI - https://doi.org/10.18632/oncotarget.28458
Correspondence to - Devalingam Mahalingam - mahalingam@northwestern.edu
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28458
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - prostate cancer, metformin, metastatic, androgen deprivation therapy, clinical trial
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
The Ride for Roswell is one of the nation’s largest cycling events—hosted by Roswell Park Comprehensive Cancer Center—to raise awareness and funds for cancer research and patient care. This charity bike ride, based out of Buffalo, New York, has brought people together for 27 years to celebrate cancer survivors, pay tribute to lives that have been lost, and to work together to support research and find a cure.
When its doors opened in Buffalo in 1898, Roswell Park Comprehensive Cancer Center was the first cancer research-focused institution in the world. Today, this institution is one of only four National Cancer Institute-designated comprehensive cancer centers in the state of New York. Roswell Park Comprehensive Cancer Center is ranked by U.S. News & World Report as one of the best cancer hospitals in the United States.
The Ride for Roswell started in 1989 when Mitch Flynn, owner of the advertising agency Flynn & Friends, met Katherine Gioia. Katherine was a four-year-old patient battling a rare form of cancer. After Katherine’s death (less than a year after her diagnosis), Katherine’s mother, Anne Gioia, and aunt, Donna Gioia, founded the Roswell Park Alliance Foundation in her memory to raise money for cancer research and treatment. On June 29, 1996, Mitch and Alliance Foundation staff launched the first Ride for Roswell.
In the 27 years since then, thanks to over 127,000 riders and thousands of volunteers, the Ride for Roswell has raised over $67 million to fund cancer research. The event has become one of the largest charity rides in the United States.
Full press release - https://www.oncotarget.net/2023/06/19/oncotarget-sponsors-2023-ride-for-roswell/
Join Team Open Access - https://give.roswellpark.org/site/TR/SpecialEvents/General?team_id=15232&pg=team&fr_id=1830
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new review paper was published in Oncotarget's Volume 14 on June 12, 2023, entitled, “ACSL4: biomarker, mediator and target in quadruple negative breast cancer.”
Breast cancer is a heterogeneous disease for which effective treatment depends on correct categorization of its molecular subtype. For the last several decades this determination has relied on hormone receptor status for estrogen, progesterone and HER2. More recently, gene expression data have been generated that further stratify both receptor-positive and receptor-negative cancers.
In this new review, researcher Marie E. Monaco from NYU Grossman School of Medicine and VA NY Harbor Healthcare System discusses the fatty acid-activating enzyme, ACSL4, which has been demonstrated to play a role in the malignant phenotype of a variety of cancers, including breast. This lipid metabolic enzyme is differentially expressed as a function of subtype in breast tumors, with highest expression observed in the mesenchymal (claudin low) and basal-like subtypes.
“ACSL4 is one of five mammalian enzyme isoforms responsible for activation (thioesterification) of long-chain fatty acids as a prerequisite to their further utilization in lipid biosynthetic and fatty acid oxidative pathways [1].”
Here, Dr. Monaco reviews data that support the potential of utilizing ACSL4 status as both a biomarker of molecular subtype and a predictor of response to a variety of targeted and non-targeted treatment regimens. The ability of ACSL4 to induce a more aggressive phenotype suggests it might be a potential target for inhibition in the treatment of breast cancer. Additional studies are needed to demonstrate the utility of this protein as both a biomarker and target in the classification and treatment of breast cancer.
“Based on these findings, we suggest 3 expanded roles for ACSL4: 1. as a biomarker for classification of breast cancer subtypes; 2. as a predictor of sensitivity to hormone-based and certain other therapies; and 3. as a target for the development of new treatment modalities.”
DOI - https://doi.org/10.18632/oncotarget.28453
Correspondence to - Marie E. Monaco - mem6@nyu.edu
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28453
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - ACSL4, breast cancer, ferroptosis, molecular subtype, quadruple negative breast cancer
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new research paper was published in Oncotarget's Volume 14 on June 12, 2023, entitled, “LP-284, a small molecule acylfulvene, exerts potent antitumor activity in preclinical non-Hodgkin's lymphoma models and in cells deficient in DNA damage repair.”
Despite advances in therapies treating non-Hodgkin’s lymphoma (NHL), 20~40% of patients experience relapsed or refractory disease. While solid tumors with homologous recombination deficiencies have been successfully targeted with synthetic lethal agents such as poly-ADP ribose polymerase (PARP) inhibitors, such synthetic lethality strategy has not yet been approved to treat patients with NHL.
In this new study, researchers Jianli Zhou, Drew Sturtevant, Cassie Love, Aditya Kulkarni, Neha Biyani, Umesh Kathad, Elizabeth Thacker, Sandeep Dave, and Kishor Bhatia from Lantern Pharma Inc., Duke University and Data Driven Bioscience investigated the mechanism of action (MoA) and therapeutic potential of a new-generation acylfulvene compound, LP-284, in both in vitro and in vivo NHL models.
“Here, we aimed to characterize LP-284’s antitumor efficacy in NHL models and further elucidate its mechanisms of action.”
One of LP-284’s MoA includes inducing the repair of double-strand DNA break (DSB). The researchers found that LP-284 exerts nanomolar potency in a panel of hematological cancer cell lines including fifteen NHL cell lines. In vivo, LP-284 treatment prolongs the survival of mantle cell lymphoma (MCL) cell line JeKo-1 derived xenograft mice by two-fold and shows increased efficacy over bortezomib and ibrutinib. In addition, LP-284 is capable of inhibiting tumor growth of JeKo-1 xenografts that are refractory to bortezomib or ibrutinib. They further showed that LP-284 is particularly lethal in cells with deficient DNA damage response and repair, a targetable vulnerability in NHL.
“In conclusion, our study has demonstrated LP-284 as a novel and potent acylfulvene drug that can suppress tumor growth in NHL models and cells with HR or TC-NER deficiency.”
DOI - https://doi.org/10.18632/oncotarget.28454
Correspondence to - Jianli Zhou - jianli@lanternpharma.com
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28454
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - non-Hodgkin's lymphoma, DNA damage, homologous recombination repair, transcription-coupled nucleotide excision repair, ATM
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new research perspective was published in Oncotarget's Volume 14 on May 19, 2023, entitled, “Targeting the Src N-terminal regulatory element in cancer.”
The signaling pathways displayed by cancer cells are often composed of the same components as the physiological ones, yet the overall result is a pathological deregulation. In this new paper, researchers Betlem Mezquita, Marjorie Reyes-Farias and Miquel Pons from the Universitat de Barcelona and Universitat Internacional de Catalunya discuss the non-receptor protein tyrosine kinase Src as a good example.
“Src, the first discovered oncogene, is the leading member of the Src family of kinases (SFK) that includes Fyn, Yes, Blk, Yrk, Fgr, Hck, Lck, and Lyn.”
Src is the first described proto-oncogene and a demonstrated player in cancer progression, as it affects proliferation, invasion, survival, cancer stemness, and drug resistance. Src activation is linked to poor prognosis in many cancer types, yet mutations in this protein are rarely observed. In addition, being a demonstrated cancer target, unspecific inhibition of the kinase activity has proven inefficient in clinics since the inhibition of Src in non-cancerous cells results in unacceptable toxicity.
Thus, there is a need for new target regions in Src that could inhibit Src activity only in certain cell types, e.g., cancer cells, while maintaining the normal physiological activity in healthy cells. The Src N-terminal regulatory element (SNRE) includes the poorly studied intrinsically disordered region with unique sequences for each of the members of the Src family. In this perspective, the researchers discuss the non-canonical regulatory mechanisms involving the SNRE and their potential use as oncotargets.
“Our group has designed a screening system to search chemical libraries for binders of the Src SNRE [88] and we are currently following up a promising lead.”
DOI: https://doi.org/10.18632/oncotarget.28434
Correspondence to: Miquel Pons - mpons@ub.edu
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28444
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords: Src family kinases, intrinsically disordered proteins, SNRE, cell-type selective drugs, drug resistance
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new research paper was published in Oncotarget's Volume 14 on May 26, 2023, entitled, “Value of chemotherapy post immunotherapy in stage IV non-small cell lung cancer (NSCLC).”
Lung cancer is the number one cause of mortality among all types of cancer worldwide. Its treatment landscape has shifted from the classic chemotherapy alone to newer regimens based on the discovery of new immunotherapy and targeted therapy drugs. However, chemotherapy is still an option for treatment of advanced non-small cell lung cancer (NSCLC) after progression on immunotherapy alone or in combination with first-line chemotherapy.
This new retrospective study, by researchers Hazem I. Assi, Maroun Bou Zerdan, Mohammad Hodroj, Makram Khoury, Nour Sabiha Naji, Ghid Amhaz, Reine Abou Zeidane, and Fadi El Karak from the American University of Beirut Medical Center and Hotel Dieu de France University Hospital, was based on chart review of patients diagnosed with advanced NSCLC cases who received Docetaxel as second or third line after being treated by immunotherapy and/or chemotherapy in previous lines. The data was collected from the medical records of physicians’ clinics in three different hospital centers in Lebanon over the period of 5 years from July 2015 until December 2020. February 2021 was data analysis cut off time.
“The main aim [of this study] was to assess the role of Docetaxel post-chemoimmunotherapy for patients with diagnosed NSCLC.”
A total of 21 patients were included in this study. The majority of our patients were males (81%). As for histologic type, most patients had non-squamous lung cancer (67%) as compared to 33% who had squamous lung cancer. Overall, their study reported a 24% response rate to Docetaxel including stable disease and partial response and a median progression free survival (PFS) of 3 months. The mean time interval elapsed from diagnosis to the initiation of Docetaxel was 11.5 months.
“New therapeutic options should be validated for the treatment of NSCLC in the second and subsequent lines of therapy considering the poor prognosis of this disease. The chemotherapy in second and third line may keep an important role in the treatment after progression on newer agents, but it needs more evidence in prospective studies including a larger number of patients.”
DOI - https://doi.org/10.18632/oncotarget.28444
Correspondence to - Fadi El Karak - Felkarak@yahoo.com
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28444
Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/
Keywords - chemotherapy, immunotherapy, non-small cell lung cancer
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new research paper was published in Oncotarget's Volume 14 on May 26, 2023, entitled, “Association of mutation and expression of the brother of the regulator of imprinted sites (BORIS) gene with breast cancer progression.”The brother of the regulator of imprinted sites (BORIS), 11 zinc-finger transcription factors, is a member of the cancer-testis antigen (CTA) family. It is mapped to chromosome number 20q13.2 and this region is genetically linked to the early onset of breast cancer. In the current study, researchers Mohammad Salman Akhtar, Naseem Akhter, Arshi Talat, Raed A. Alharbi, Abdulmajeed A.A. Sindi, Faisal Klufah, Hanan E. Alyahyawi, Abdulmohsen Alruwetei, Abrar Ahmad, Mazin A. Zamzami, SVS Deo, Syed Akhtar Husain, Osama A. Badi, and Mohammad Jahir Khan from Al-Baha University, Jamia Millia Islamia, ITS Dental College, Qassim University, King Abdulaziz University, All India Institute of Medical Sciences (AIIMS), Henry Ford Health System, and Jawahar Lal Nehru University analyzed the correlation between BORIS mutations and the expression of the protein in breast cancer cases.“The present study is to find out the mutations of BORIS genes in hot spot exons by PCR-SSCP and by automated DNA sequencing in breast cancer tissue samples along with adjacent normal samples.”A population-based study including a total of 155 breast cancer tissue samples and an equal number of normal adjacent tissues from Indian female breast cancer patients was carried out. Mutations of the BORIS gene were detected by polymerase chain reaction-single standard confirmation polymorphisms (PCR-SSCP) and automated DNA sequencing and by immunohistochemistry for BORIS protein expression were performed. The observed findings were correlated with several clinicopathological parameters to find out the clinical relevance of associations.“The BORIS mutations and high protein expression occur frequently in carcinoma of the breast suggesting their association with the onset and progression of breast carcinoma. Further, the BORIS has the potential to be used as a biomarker.”DOI - https://doi.org/10.18632/oncotarget.28442Correspondence to - Mohammad Salman Akhtar - mdsalmanakhtar@yahoo.com, milyas@bu.edu.saSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28442Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - BORIS, breast cancer, mutation, transcription factor, PCR-SSCPAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research paper was published in Oncotarget's Volume 14 on May 26, 2023, entitled, “Deconstructing the role of MALAT1 in MAPK-signaling in melanoma: insights from antisense oligonucleotide treatment.”The long non-coding RNA (lncRNA) MALAT1 is a regulator of oncogenesis and cancer progression. MAPK-pathway upregulation is the main event in the development and progression of human cancer, including melanoma and recent studies have shown that MALAT1 has a significant impact on the regulation of gene and protein expression in the MAPK pathway. However, the role of MALAT1 in regulation of gene and protein expression of the MAPK-pathway kinases RAS, RAF, MEK, and ERK in melanoma is largely unknown. In this study, researchers Valentin Feichtenschlager, Yixuan James Zheng, Wilson Ho, Linan Chen, Ciara Callanan, Christopher Chen, Albert Lee, Jose Ortiz, Klemens Rappersberger, and Susana Ortiz-Urda from the University of California San Francisco and Medical University Vienna demonstrated the impacts of antisense oligonucleotide (ASO)-based MALAT1-inhibition on MAPK-pathway gene regulation in melanoma. “Our results showed that MALAT1-ASO treatment decreased BRAF RNA expression and protein levels, and MALAT1 had increased correlation with MAPK-pathway associated genes in melanoma patient samples compared to healthy skin.”Additionally, drug-induced MAPK inhibition upregulated MALAT1-expression, a finding that resonates with a paradigm of MALAT1-expression presented in this work: MALAT1 is downregulated in melanoma and other cancer types in which MALAT1 seems to be associated with MAPK-signaling, while MALAT1-ASO treatment strongly reduced the growth of melanoma cell lines, even in cases of resistance to MEK inhibition. MALAT1-ASO treatment significantly inhibited colony formation in vitro and reduced tumor growth in an NRAS-mutant melanoma xenograft mouse model in vivo, while showing no aberrant toxic side effects. “Our findings demonstrate new insights into MALAT1-mediated MAPK-pathway gene regulation and a paradigm of MALAT1 expression in MAPK-signaling-dependent cancer types. MALAT1 maintains essential oncogenic functions, despite being downregulated.”DOI - https://doi.org/10.18632/oncotarget.28447Correspondence to - Valentin Feichtenschlager - valentin.feichtenschlager@ucsf.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28447Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - MALAT1, MAPK-pathway, BRAF, melanoma, antisense oligonucleotidesAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Blog summary: “Role of creatine shuttle in colorectal cancer cells.”_____________________________________________Since the 1992 Barcelona Olympics, creatine supplementation has increased in popularity and grown to widespread use among the mainstream public. Creatine is a naturally occurring compound, primarily stored in skeletal muscle and involved in energy production for high-intensity activities—enhancing performance and supporting muscle growth and strength. The process by which creatine is transported into the muscles and utilized for energy production is referred to as the creatine shuttle. While it is a useful mechanism for healthy muscles, the creatine shuttle has also been implicated in cancer.“The creatine shuttle is highlighted in cancer as a source of energy for cancer cells that display aggressive proliferation, and aberrant creatine kinase (CK) levels are known to be associated with many malignancies and mitotic control [7].”In a new study, researchers Mayu Kita, Rina Fujiwara-Tani, Shingo Kishi, Shiori Mori, Hitoshi Ohmori, Chie Nakashima, Kei Goto, Takamitsu Sasaki, Kiyomu Fujii, Isao Kawahara, Ujjal Kumar Bhawal, Yi Luo, and Hiroki Kuniyasu from Nara Medical University, Saveetha University and Nantong University hypothesized that the creatine shuttle is involved in energy metabolism and other adenosine triphosphate (ATP) supply in cancer cells. On May 19, 2023, their new research paper was published in Oncotarget’s Volume 14, entitled, “Role of creatine shuttle in colorectal cancer cells.”Full blog - https://www.oncotarget.org/2023/05/25/can-the-creatine-shuttle-be-targeted-to-fight-colorectal-cancer/DOI - https://doi.org/10.18632/oncotarget.28436Correspondence to - Hiroki Kuniyasu - cooninh@zb4.so-net.ne.jp, and Rina Fujiwara-Tani - rina_fuji@naramed-u.ac.jpSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28436Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - creatine kinase B, mitochondrial creatine kinase, ATP metabolism, phosphorylation signal, stemnessAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Dr. Gopal C. Kundu from KIIT Deemed to be University in Odisha, India, describes a recent editorial he co-authored that was published by Oncotarget in Volume 14, entitled, “The molecular dialogue between the tumor cells and fibroblasts.”DOI - https://doi.org/10.18632/oncotarget.28405Correspondence to - Gopal C. Kundu - gopalc.kundu@kiit.ac.inSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28405Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - CAFs, heterogeneity, myofibroblasts, drug resistance, osteopontinAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research perspective was published in Oncotarget's Volume 14 on May 10, 2023, entitled, “HER3- A key survival pathway and an emerging therapeutic target in metastatic colorectal cancer and pancreatic ductal adenocarcinoma.”Colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) are highly metastatic cancers with poor survival rates. The tumor microenvironment has been shown to play a critical role in cancer progression and response to therapies. Endothelial cells (ECs) are a key component of the tumor microenvironment and promote cancer cell survival by secreting soluble factors that activate cancer-promoting signaling pathways. In this new perspective, researchers Omkar Desai and Rui Wang from Case Western Reserve University and University Hospitals Cleveland Medical Center discuss their studies and others that have identified HER3 as a key mediator of liver EC-induced chemoresistance and cancer cell growth in metastatic CRC and PDAC. “In complement to our studies, prior preclinical studies have shown that HER3-targeted therapies with antibodies and inhibitors have been effective in blocking tumor growth in several types of cancers [22, 23], specifically breast cancer [24], head and neck squamous cell carcinoma (HNSCC) [25], PDAC [25], and non-small cell lung cancer (NSCLC) [26]. However, translating the preclinical findings to clinical studies has shown limited impact on patient outcomes.”In this article, the researchers discuss that HER3-targeted therapies may be effective in treating patients with HER3-expressing CRC and PDAC, and highlight the importance of applying HER3 expression as a predictive biomarker for patient response to HER3-targeted therapies. They also discuss the challenges encountered in past clinical trials of HER3-targeted therapies, including the role of NRG1 gene fusions, alternative HER3 activation mechanisms, and adaptive resistance mechanisms. Finally, the team concludes by suggesting the future directions of HER3-targeted therapies, including novel approaches to overcome chemoresistance and promote cancer cell death.“In summary, we discovered that the surrounding liver EC microenvironment plays a key role in activating HER3 and promoting cell survival in mCRC and mPDAC, and potentially other types of cancer that metastasize to the liver.”DOI - https://doi.org/10.18632/oncotarget.28421Correspondence to - Rui Wang - rxw517@case.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28421Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - HER3, colorectal, pancreatic cancer, metastasis, microenvironmentAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research paper was published in Oncotarget's Volume 14 on May 19, 2023, entitled, “G-protein-coupled receptor 141 mediates breast cancer proliferation and metastasis by regulating oncogenic mediators and the p-mTOR/p53 axis.”Breast cancer morbidity is surging towards the peak in females across the globe. An inherent property of cancer cells is enhanced cell proliferation rate and migration capability, leading to deregulated cell signaling cascades. G-protein-coupled receptors (GPCRs) have recently emerged as a hot-spot target in cancer research.Researchers Monalisa Parija, Amit K. Adhya and Sandip K. Mishra from the Institute of Life Sciences, Regional Centre for Biotechnology and All India Institute of Medical Sciences identified aberrant expression of G-protein-coupled receptor 141 (GPR141) in different breast cancer subtypes that correlate with poor prognosis. However, the molecular mechanism via which GPR141 advances breast cancer remains elusive. Increased GPR141 expression enhances the migratory behavior of breast cancer, driving oncogenic pathways both in vitro and in vivo through activation of epithelial to mesenchymal transition (EMT), oncogenic mediators and regulation of p-mTOR/p53 signaling. “Our study unveils a molecular mechanism for p53 downregulation and activation of p-mTOR1 and its substrates in GPR141 overexpressed cells, accelerating breast tumorigenesis.”In their current study, the researchers found that an E3 ubiquitin ligase, Cullin1, partly mediates p53 degradation via proteasomal pathway. Co-immunoprecipitation results show that the phosphorylated form of 40S ribosome protein S6 (ps6., a p-mTOR1 substrate) forms a complex with Cullin1. These findings suggest an interplay between Cullin1 and p-mTOR1 in GPR141 overexpressed cells that downregulates p53 expression, thus inducing tumor growth. GPR141 silencing restores p53 expression and attenuates p-mTOR1 signaling events, thereby impeding proliferation and migration in breast cancer cells. Their findings describe the role of GPR141 in breast cancer proliferation, and metastasis, as well as in influencing the tumor microenvironment. Modulating GPR141 expression could pave the way for a better therapeutic approach to regulating breast cancer progression and metastasis.“In conclusion, our research highlights the gain of function of GPR141 drives breast tumorigenesis by inducing tumor cell properties via the p-mTOR1/p53 axis, altering EMT markers, and enhancing oncogenic mediators.”DOI - https://doi.org/10.18632/oncotarget.28433Correspondence to - Sandip K. Mishra - sandipkmishra@ils.res.inSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28433Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - G-protein-coupled receptor 141, cell migration, metastasis, p-mTOR, p53About OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research perspective was published in Oncotarget's Volume 14 on May 4, 2023, entitled, “Targeting cellular respiration as a therapeutic strategy in glioblastoma.”While glycolysis is abundant in malignancies, mitochondrial metabolism is significant as well. Mitochondria harbor the enzymes relevant for cellular respiration, which is a critical pathway for both regeneration of reduction equivalents and energy production in the form of ATP.In this research perspective, researchers Enyuan Shang, Trang Thi Thu Nguyen, Mike-Andrew Westhoff, Georg Karpel-Massler, and Markus D. Siegelin from Columbia University Medical Center, City University of New York and Ulm University Medical Center discuss their recent finding that FDA-approved HDAC-inhibitors may have a profound impact on energy metabolism in solid tumor cells, including glioblastoma (GBM). “Because of the impact of HDAC-inhibitors on metabolism we hypothesized that imipridones, which suppress cellular respiration, might synergize with these compounds to significantly enhance killing of GBM cells [38]. Indeed, we found that imipridones reversed HDAC-inhibitor induced activation of cellular respiration and in turn the combination treatment facilitated induction of intrinsic apoptosis in a manner that was partially reliant on the anti-apoptotic Bcl-2 family members.”The oxidation of NADH2 and FADH2 are fundamental since NAD and FAD are the key components of the TCA-cycle that is critical to entertain biosynthesis in cancer cells. The TCA-cycle itself is predominantly fueled through carbons from glucose, glutamine, fatty acids and lactate. Targeting mitochondrial energy metabolism appears feasible through several drug compounds that activate the CLPP protein or interfere with NADH-dehydrogenase, pyruvate-dehydrogenase, enzymes of the TCA-cycle and mitochondrial matrix chaperones. While these compounds have demonstrated anti-cancer effects in vivo, recent research suggests which patients most likely benefit from such treatments.“In summary, targeting tumor cell metabolism is relevant and future research needs to identify patient populations that particularly benefit from such treatments. Moreover, while most studies related to metabolism still rest predominantly on the tumor cells it is critical to extend such observations to the microenvironment of the tumors, especially with regards to the immune system [41, 42].”DOI - https://doi.org/10.18632/oncotarget.28424Correspondence to - Markus D. Siegelin - ms4169@cumc.columbia.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28424Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - glioblastoma, metabolism, lactate, carbon tracing, central carbon metabolismAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Impact Journals (Oncotarget's publisher) will be participating as an exhibitor at the Society for Scholarly Publishing (SSP) 45th Annual Meeting, which convenes on May 31–June 2, 2023, at the Oregon Convention Center & Hyatt Regency Portland in Portland, Oregon, USA. This year, the SSP’s meeting theme is: “Transformation, Trust, and Transparency.”“The pace of change in our industry continues unabated, with seismic shifts in areas such as the dissemination of research, business models, and the nature of the workplace. And yet, while pressure for change has become the new normal, fundamental change has proved more elusive. We invite you to join us in highlighting the Trust and Transparency issues that underlie many of the challenges we face and exploring what it takes to create more meaningful Transformation in scholarly publishing.” (Source: sspnet.org)Visit booth No. 216 at the SSP 45th Annual Meeting to connect with members of the Impact Journals team.About Impact Journals:Impact Journals publishes scholarly journals in the biomedical sciences with a focus on all areas of cancer and aging research. Our mission is to provide scientists with the opportunity to share their exceptional discoveries, to offer services that enable rapid dissemination of results, and to present vital findings from the many fields of biomedical science. Our goal is life without disease.To learn more about Impact Journals, visit www.ImpactJournals.com.Connect with us on social media to stay updated on journals published by Impact Journals: Oncotarget Twitter – https://twitter.com/Oncotarget Aging Twitter – https://twitter.com/AgingJrnl Oncotarget Facebook – https://www.facebook.com/Oncotarget Aging Facebook – https://www.facebook.com/AgingUS Oncotarget YouTube – https://www.youtube.com/@OncotargetJournal Aging YouTube – https://www.youtube.com/@AgingJournal Oncotarget LinkedIn – https://www.linkedin.com/company/oncotarget/ Aging LinkedIn – https://www.linkedin.com/company/agingFor media requests, please contact media@impactjournals.com.
A new research paper was published in Oncotarget's Volume 14 on May 12, 2023, entitled, “Development and implementation of an automated and highly accurate reporting process for NGS-based clonality testing.”B and T cells undergo random recombination of the VH/DH/JH portions of the immunoglobulin loci (B cell) and T-cell receptors before becoming functional cells. When one V-J rearrangement is over-represented in a population of B or T cells indicating an origin from a single cell, this indicates a clonal process. Clonality aids in the diagnosis and monitoring of lymphoproliferative disorders and evaluation of disease recurrence. In a new study, researchers Sean T. Glenn, Phillip M. Galbo Jr., Jesse D. Luce, Kiersten Marie Miles, Prashant K. Singh, Manuel J. Glynias, and Carl Morrison from Roswell Park Comprehensive Cancer Center aimed to develop objective criteria, which can be automated, to classify B and T cell clonality results as positive (clonal), No evidence of clonality, or invalid (failed). “Using clinical samples with “gold standard” clonality data obtained using PCR/CE testing, we ran NGS-based amplicon clonality assays and developed our own model for clonality reporting.”To assess the performance of their model, the researchers analyzed the NGS results across other published models. Their model for clonality calling using NGS-based technology increases the assay’s sensitivity, more accurately detecting clonality. In addition, they built a computational pipeline to use their model to objectively call clonality in an automated fashion. “Collectively the results outlined below will have a direct clinical impact by expediting the review and sign-out process for concise clonality reporting.”DOI - https://doi.org/10.18632/oncotarget.28429Correspondence to - Sean T. Glenn - Sean.Glenn@RoswellPark.orgSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28429Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - clonality, NGS, bioinformatics, molecular diagnostics, leukemiaAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Blog summary: “From the groin to the brain: a transfemoral path to blood-brain barrier opening.”___________________________________________Just a small number of molecules, including alcohol and caffeine, are able to cross the blood-brain barrier (BBB). The BBB is a highly selective semipermeable membrane that separates circulating blood from extracellular fluid in the brain. It plays a critical role in protecting the brain from harmful substances in the blood while also maintaining a stable and consistent environment for neuronal function. Without the BBB, humans would be at the mercy of any harmful toxin, pathogen and unwanted substance that could cross from the bloodstream into the brain.This protective function also makes it difficult to deliver therapeutic agents to the brain, as the majority of drugs and other molecules are unable to cross the BBB. This is particularly problematic for the treatment of brain-localized diseases, including brain cancers and neurological disorders, which require high concentrations of drugs to effectively target sites in the brain. In a new editorial paper, researchers Thomas C. Chen, Weijun Wang and Axel H. Schönthal from the University of Southern California‘s Keck School of Medicine discuss a series of preclinical studies that introduced the novel concept of intraarterial (IA) injection of NEO100—a promising strategy aimed at temporarily and safely opening the BBB up for therapeutic treatment. Their editorial was published in Oncotarget’s Volume 14 on May 4, 2023, entitled, “From the groin to the brain: a transfemoral path to blood-brain barrier opening.”“It is believed that procedures to open the BBB in a controlled and safe fashion might provide tremendous advantages by allowing optimal brain entry of any and all circulating therapeutics.”Full blog - https://www.oncotarget.org/2023/05/11/reaching-the-brain-through-the-groin-a-novel-approach-to-brain-cancer/Paper DOI - https://doi.org/10.18632/oncotarget.28414Correspondence to - Thomas C. Chen - thomas.chen@med.usc.edu, and Axel H. Schönthal - schontha@usc.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28414Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - brain metastases, glioma, NEO100, perillyl alcohol, transfemoral cannulationAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research perspective was published in Oncotarget's Volume 14 on May 4, 2023, entitled, “Using cancer proteomics data to identify gene candidates for therapeutic targeting.”Gene-level associations obtained from mass-spectrometry-based cancer proteomics datasets represent a resource for identifying gene candidates for functional studies. In their new research perspective, researchers Diana Monsivais, Sydney E. Parks, Darshan S. Chandrashekar, Sooryanarayana Varambally, and Chad J. Creighton from Baylor College of Medicine and University of Alabama at Birmingham discuss their recent study where they surveyed proteomic correlates of tumor grade across multiple cancer types and identified specific protein kinases having a functional impact on uterine endometrial cancer cells. “This previously published study provides just one template for utilizing public molecular datasets to discover potential novel therapeutic targets and approaches for cancer patients.”Proteomic profiling data combined with corresponding multi-omics data on human tumors and cell lines can be analyzed in various ways to prioritize genes of interest for interrogating biology. Across hundreds of cancer cell lines, CRISPR loss of function and drug sensitivity scoring can be readily integrated with protein data to predict any gene’s functional impact before bench experiments are carried out. Public data portals make cancer proteomics data more accessible to the research community. Drug discovery platforms can screen hundreds of millions of small molecule inhibitors for those that target a gene or pathway of interest. “Here, we discuss some of the available public genomic and proteomic resources while considering approaches to how these could be leveraged for molecular biology insights or drug discovery. We also demonstrate the inhibitory effect of BAY1217389, a TTK inhibitor recently tested in a Phase I clinical trial for the treatment of solid tumors, on uterine cancer cell line viability.”DOI: https://doi.org/10.18632/oncotarget.28420Correspondence to: Chad J. Creighton - creighto@bcm.edu Sign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28402Subscribe for free publication alerts from Oncotarget: https://www.oncotarget.com/subscribe/Keywords: proteomics, proteogenomics, multi-omics, cancer, TTK protein kinaseAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Dr. Georg F. Weber, from the University of Cincinnati Academic Health Center, describes a research perspective he authored that was published by Oncotarget in Volume 14, entitled, “Crossroads: the role of biomarkers in the management of lumps in the breast.”DOI - https://doi.org/10.18632/oncotarget.28402Correspondence to - Georg F. Weber - georg.weber@uc.eduAbstractPremalignant lesions in the breast pose a difficult decision-making problem, whether to treat proactively and accept the side effects or to engage in watchful waiting and possibly encounter a later diagnosis of invasive cancer. A biomarker or set of biomarkers to inform on the individual progression risk would be beneficial to the patient and cost-effective for the healthcare system. The gene products of tumor progression may be expressed in early non-cancerous (“premalignant”) lesions, where they are associated with a high probability for full transformation in breast cancers. One such molecule is the OPN splice variant-c. OPN-c is also present in a fraction of the premalignant lesions, where it reflects an elevated risk for progression to cancer within 5 years, regardless of the lesion’s subtype. This marker has the properties needed to facilitate decisions to treat at the premalignant stage.Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28402Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - breast cancer premalignant lesion, biomarker, biopsy, mammographyAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research paper was published in Oncotarget's Volume 14 on May 4, 2023, entitled, “Human LY6 gene family: potential tumor-associated antigens and biomarkers of prognosis in uterine corpus endometrial carcinoma.”The human Lymphocyte antigen-6 (LY6) gene family has recently gained interest for its possible role in tumor progression. In this new study, researchers Luke A. Rathbun, Anthony M. Magliocco and Anil K. Bamezai from Villanova University carried out in silico analyses of all known LY6 gene expression and amplification in different cancers using TNMplot and cBioportal. In addition, the team analyzed patient survival by Kaplan-Meier plotter after mining the TCGA database. “We report that upregulated expression of many LY6 genes is associated with poor survival in uterine corpus endometrial carcinoma (UCEC) cancer patients.” Importantly, the expression of several LY6 genes is elevated in UCEC when compared to the expression in normal uterine tissue. For example, LY6K expression is 8.25× higher in UCEC compared to normal uterine tissue, and this high expression is associated with poor survival with a hazard ratio of 2.42 (p-value = 0.0032). Therefore, some LY6 gene products may serve as tumor-associated antigens in UCEC, biomarkers for UCEC detection, and possibly targets for directing UCEC patient therapy. “Further analysis of tumor-specific expression of LY6 gene family members and LY6-triggered signaling pathways is needed to uncover the function of LY6 proteins and their ability to endow tumor survival and poor prognosis in UCEC patients.”DOI - https://doi.org/10.18632/oncotarget.28409Correspondence to - Anil K. Bamezai - anil.bamezai@villanova.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28409Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - LY6 gene family, uterine cancer, tumor-associated antigen, patient survival, biomarkerAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new review paper was published in Oncotarget's Volume 14 on April 26, 2023, entitled, “Systemic AL amyloidosis: current approach and future direction.”In this review, researchers Maroun Bou Zerdan, Lewis Nasr, Farhan Khalid, Sabine Allam, Youssef Bouferraa, Saba Batool, Muhammad Tayyeb, Shubham Adroja, Mahinbanu Mammadii, Faiz Anwer, Shahzad Raza, and Chakra P. Chaulagain from SUNY Upstate Medical University, University of Texas MD Anderson Cancer Center, Monmouth Medical Center, University of Balamand, Cleveland Clinic Ohio, UnityPoint Methodist, Houston Methodist Cancer Center, and Cleveland Clinic Florida report the literature on the latest treatment updates of Systemic Light chain (AL) amyloidosis and the ongoing clinical trials highlighting the future treatments.“In this manuscript, we discuss the general approach towards treating patients with amyloidosis and dive into the future perspectives in this multi-systemic disease.”Systemic AL amyloidosis is a monoclonal plasma cell proliferative disorder characterized by deposition of amyloidogenic monoclonal light chain fragments causing organ dysfunction. It is a fatal disease and if not diagnosed and treated early can lead to organ failure and potentially death. The renal system along with the cardiovascular system are the most common organs involved, but other organs such as the gut and liver can be involved as well. The initial evaluation of patients requires confirming the diagnosis with tissue biopsy and staining with Congo red followed by confirmatory typing with mass spectrometry of the Congo red positive tissue. Then establishing the extent of the organs involvement by various staging and biomarkers testing. The treatment options and the tolerability of therapy depend on the disease staging, frailty and co-morbidities. The autologous hematopoietic cell transplantation (HCT) after high dose melphalan therapy is an effective strategy which is usually done after initial bortezomib induction therapy. Unfortunately, most systemic AL amyloidosis patients are not candidates for HCT due to frailty, old age, multi-organ involvement, and renal or heart failure at the time of diagnosis. While it is widely accepted that the patients need to be treated until they achieve complete hematologic response, the maintenance therapy after HCT is not well established in AL amyloidosis. “The relationship between AL amyloidosis and MGUS is less clear, but some studies suggest that the risk of developing AL amyloidosis may be increased in patients with MGUS. It is important for patients with these conditions to undergo regular monitoring and evaluation for signs of AL amyloidosis, as early diagnosis and treatment can improve outcomes.”DOI - https://doi.org/10.18632/oncotarget.28415Correspondence to - Chakra P. Chaulagain - chaulac@ccf.orgSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28415Keywords - amyloidosis, managementAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research perspective was published in Oncotarget's Volume 14 on April 26, 2023, entitled, “Disruption of retinol-mediated IL-6 expression in colon cancer-associated fibroblasts: new perspectives on the role of vitamin A metabolism.”Colon cancer (CRC) is one of the most common malignancies and is a leading cause of cancer-related deaths worldwide. While the tumor microenvironment (TME) supports tumor growth and immune escape through tumor-promoting inflammation, the mechanisms by which the TME promotes CRC are far from being elucidated. Stromal myo-/fibroblasts (MFs) account for up to 30% of lamina propria cells in the normal human colon and their number is dramatically increased in CRC. Fibroblasts from cancers, also known as cancer-associated fibroblasts (CAFs), differ from normal colonic MF (N-MFs) and support tumor-promoting inflammation, in part due to increased IL-6 secretion. CAFs are very abundant in the TME and are among the major cells involved in tumor inflammation and progression. In this research perspective, researchers Romain Villéger, Marina Chulkina, Randy C. Mifflin, Don W. Powell, and Irina V. Pinchuk from the Université de Poitiers, Penn State Health Milton S. Hershey Medical Center and The University of Texas Medical Branch highlight recent data obtained regarding IL-6 regulation in colorectal cancer CAFs through vitamin A (retinol) metabolism, discuss current limitations in our understanding of the mechanisms leading to the CAF pro-inflammatory phenotype, and discuss potential approaches to target CAF retinoid metabolism during CRC treatment."While the overall mechanisms responsible for the IL-6 increase within the CRC tumor stroma remain to be elucidated, our study highlights the crucial role of stromal vitamin A pathway in IL-6 regulation."DOI: https://doi.org/10.18632/oncotarget.28399Correspondence to - Iryna V. Pinchuk - ipinchuk@pennstatehealth.psu.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28399Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - tumor microenvironment, colon cancer, inflammation, fibroblasts, IL-6About OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research perspective was published in Oncotarget's Volume 14 on April 24, 2023, entitled, “Crossroads: the role of biomarkers in the management of lumps in the breast.”Here, Dr. Georg F. Weber from the University of Cincinnati Academic Health Center discusses a long-standing issue in women’s health: lumps in the breast. Women over the age of 40 years often have lumps in their breasts that are not cancerous at the time of biopsy (comprising atypias, hyperplasias, papillomas, radial scars, lobular carcinoma in situ, ductal carcinoma in situ (DCIS)). These premalignant lesions in the breast pose a difficult decision-making problem, whether to treat proactively and accept the side effects or to engage in watchful waiting and possibly encounter a later diagnosis of invasive cancer. These patients need to make the difficult decision whether to treat the lesions proactively and accept the substantial compromise in their quality of life (from surgery, radiation, or hormone therapy: Surgery often ensues for definitive diagnosis. Radiation may follow the surgical resection of DCIS by lumpectomy. Hormone therapy can come into play as a strategy for risk reduction if the estimated 5-year risk exceeds 1.6% in the Gail model [2]) or to engage in watchful waiting and risk a later diagnosis of invasive cancer (the proverbial sword of Damocles). Currently, two forms of assessment are available to facilitate making that choice.Decades of cancer diagnosis and treatment have achieved substantial improvements. Yet, with every milestone of progress, new needs have surfaced. Breast care is privileged to have the availability of mammography and biopsy to assess the propensities of lumps. “A meaningful next step needs to entail biomarker development, pointing the way toward either preemptive treatment or watchful waiting at the crossroad.”DOI: https://doi.org/10.18632/oncotarget.28402Correspondence to - Georg F. Weber - georg.weber@uc.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28402Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - breast cancer premalignant lesion, biomarker, biopsy, mammographyAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Listen to a blog summary of an editorial perspective that was published in Oncotarget’s Volume 14, entitled, “EGFR endocytosis: more than meets the eye.”_________________________________EGFR (epidermal growth factor receptor) is a crucial protein that plays a significant role in various biological processes such as cell growth, proliferation, differentiation, and survival. Dysregulation of EGFR signaling has been implicated in the development and progression of numerous human cancers, including lung, breast and colon cancer. Therefore, EGFR has emerged as an attractive target for cancer therapy, and several drugs that target EGFR are in clinical use or under investigation.In recent years, endocytosis, the process by which cells internalize molecules and transport them into intracellular compartments, has emerged as a critical modulator of EGFR signaling. Endocytosis of EGFR not only regulates the duration and intensity of EGFR signaling but also modulates the signaling output. Dysregulation of EGFR endocytosis has been implicated in the development of drug resistance to EGFR-targeted therapies, highlighting the importance of understanding the mechanisms that regulate EGFR endocytosis.In a new editorial perspective, researchers Aysegul Sapmaz and Ayse Elif Erson-Bensan from Middle East Technical University provide an overview of the recent advances in our understanding of EGFR endocytosis and its role in EGFR signaling and cancer. The authors highlight the importance of the dynamic interplay between EGFR endocytosis and downstream signaling pathways and discuss how aberrant EGFR endocytosis contributes to drug resistance to EGFR-targeted therapies. On April 10, 2023, their editorial perspective was published in Oncotarget’s Volume 14, entitled, “EGFR endocytosis: more than meets the eye.”“Here we review the role of the EGF-SNX3-EGFR axis in breast cancers with an extended discussion on deregulated EGFR endocytosis in cancer.”Full blog - https://www.oncotarget.org/2023/04/27/defining-the-complexity-of-egfr-endocytosis-in-cancer/Paper DOI - https://doi.org/10.18632/oncotarget.28400Correspondence to - Ayse Elif Erson-Bensan - erson@metu.edu.trSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28400Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - EGFR, SNX3, USP32, endocytosis, cancer, breast cancerAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research paper was published in Oncotarget's Volume 14 on April 24, 2023, entitled, “Differential silencing of STAT3 isoforms leads to changes in STAT3 activation.”Signal transducer and activator of transcription 3 (STAT3) is a transcription factor involved in multiple fundamental biological processes and a key player in cancer development and progression. STAT3 is activated upon tyrosine phosphorylation and is constitutively active in various malignancies; therefore, the expression of phospho-STAT3 (pSTAT3) has been recognized as a predictor of poor survival. STAT3 encodes two alternatively-spliced STAT3 isoforms: the full-length STAT3α isoform and the truncated STAT3β isoform. These isoforms have been suggested as the reason for the occasionally observed opposing roles of STAT3 in cancer: an oncogene, on one hand, and a tumor suppressor on the other. In this new study, researchers Inbal Shamir, Ilan Tsarfaty, Gidi Paret, and Yael Nevo-Caspi from Sheba Medical Center and Tel Aviv University investigated the roles of STAT3α and STAT3β in aggressive breast cancer. They manipulated endogenous STAT3 isoform expression and measured outcomes to mimic physiological changes more accurately. “In this study we examined the roles of STAT3 isoforms using specific siRNAs that target either STAT3α or STAT3β. We used the MDA-MB-231 cell line which represents an aggressive and mortal subtype of breast cancer, in which STAT3 is overexpressed and constitutively activated [14].”The team separately silenced each isoform in the MDA-MB-231 cell line and found that they affect each other’s activation, impacting cell viability, cytokine expression, and migration. Their results show that each of the isoforms affects the activation (i.e., phosphorylation) of the other isoform and leads to changes in the outcome of the cells. They conclude that both STAT3α and STAT3β play a crucial role in the function of STAT3. Distinguishing between the two isoforms and their active forms is crucial for STAT3-related cancer diagnosis and therapy.“Referring to STAT3 as a single protein can lead to wrong conclusions, as they have different functions. Current STAT3 inhibitors target both isoforms, but this approach should be revised for better patient care. We present an endogenous mechanism that can shift the balance in a favorable direction, and we suggest developing treatments that mimic this mechanism could lead to new avenues for cancer therapy.”DOI: https://doi.org/10.18632/oncotarget.28412Correspondence to - Yael Nevo-Caspi - yael.caspi@sheba.health.gov.ilKeywords - STAT3: Signal transducer and activator of transcription 3, ER: endoplasmic reticulum, TAD: transactivation domain, SH2: Src homology 2, RQ: Relative quantitativeSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28412Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/About OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new editorial paper was published in Oncotarget's Volume 14 on April 10, 2023, entitled, “Tumor necroptosis promotes metastasis through modulating the interplay between tumor and host immunity.”In this new editorial, researchers Zhaoshan Liu, Swati Choksi and Zheng-Gang Liu from the National Institutes of Health’s National Cancer Institute discuss cell death—which can happen as finely regulated programmed cell death (PCD) or non-regulated accidental cell death (necrosis). In addition to apoptosis, which is the first known PCD, several other forms of PCD such as necroptosis and ferroptosis have been identified and the underlying mechanisms of these forms of cell death have been well studied. For necroptosis, a regulated necrotic cell death, Mixed lineage kinase domain-like protein (MLKL) was found to be the key executor of the death process and its oligomerization and translocation to the plasma membrane results in the shedding of cell surface proteins and the rupture of the cell plasma membrane of necroptotic cells. The role of the different forms of PCD in tumorigenesis has been extensively investigated. While apoptosis and ferroptosis inhibit tumor progression, necroptosis seems to have a promoting role in tumor progression. The researchers here recently found that necroptosis is the main form of cell death observed in tumor necrosis, the foci of cell death in core regions of solid tumors under hypoxia and nutrient deprivation. More importantly, they found that blocking necroptosis leads to the inhibition of metastasis in mouse breast cancer models.“Developing novel necroptosis inhibitor[s] by targeting other proteins such as MLKL may be critical for successfully blocking necroptosis in cancer and mitigating metastasis.”Full editorial: DOI: https://doi.org/10.18632/oncotarget.28404 Correspondence to - Zheng-Gang Liu - zgliu@helix.nih.govSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28404Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - necroptosis, breast cancer, metastasis, E-cadherin, immunityAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research paper was published in Oncotarget's Volume 14 on April 15, 2023, entitled, “Importance of carbohydrate antigen (CA 19-9) and carcinoembrionic antigen (CEA) in the prognosis of patients with duodenal adenocarcinoma: a retrospective single-institution cohort study.”Duodenal adenocarcinoma (DA) is a rare malignancy without validated tumor markers. In practice, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) are often used in the management of DA, though their prognostic value is unknown.In this new study, researchers Ellery Altshuler, Raymond Richhart, William King, Mahmoud Aryan, Akash Mathavan, Akshay Mathavan, Keegan Hones, Daniel Leech, Logan Pucci, Joshua Riklan, Pat Haley, Ilyas Sahin, Brian Ramnaraign, Sherise Rogers, Ibrahim Nassour, Steven Hughes, Thomas J. George, and Jesus Fabregas from the University of Florida, University of Florida Health Cancer Center and University of Alabama at Birmingham conducted a single-institution retrospective review including patients diagnosed with biopsy-confirmed adenocarcinoma of the duodenum between 2006 and 2021. “To our knowledge, this is the first study to evaluate the role of tumor markers in patients with DA. In fact, this is the largest single institution study in the US evaluating this disease.”Peri-ampullary tumors were excluded. Levels of CA 19-9 and CEA were collected as continuous variables and were analyzed as binary variables: normal vs. high, using the maximum normal value as a cut-off (normal Ca 19-9 <35 U/ml; CEA <3 ng/ml). Survival analysis was conducted using Kaplan Meier curves, log-rank test and Cox proportional hazards model.There were 68 patients included in the final analysis. Median age was 67 years old and median follow-up time was 22.2 months. CA 19-9 and CEA were elevated in 36.8% and 48.5% of patients, respectively. A concomitant elevation of both tumor markers was associated with worsened OS (HR 2.140, 95% CI: 1.114–4.112; p = 0.019). After controlling for age and sex on multivariate analysis, elevation in both CA 19-9 ≥35 and CEA ≥3.0 remained significantly associated with increased mortality (HR 2.278, 95% CI: 1.162–4.466; p = 0.016).“In summary, CA 19-9 and, to a lesser extent, CEA, show promise as prognostic markers in DA. Larger studies are needed to validate their use and to evaluate their performance as markers of recurrence.”DOI: https://doi.org/10.18632/oncotarget.28406 Correspondence to: Ellery Altshuler - ellery.maya-altshuler@medicine.ufl.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28406Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - DA: duodenal adenocarcinoma, CEA: carcinoembryonic antigen, CA, carbohydrate antigenAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Listen to a blog summary of an editorial published in Oncotarget on March 21, 2023, entitled, “Therapy drives genomic evolution in metastatic cancer._________________________________________________There are several theories that attempt to explain the genesis of cancer. One prominent theory is the genetic theory—proposing that cancer may arise from the accumulation of genetic mutations that alter the normal functioning of cells. These mutations can drive the formation of tumors, which can then spread to other parts of the body in a process known as metastasis. Metastatic cancer is often difficult to treat because it has evolved to become resistant to standard therapies. “It is generally accepted that development of cancer is a slow process, likely spanning decades during which the developing neoplastic cells sequentially acquire genomic alterations that will eventually give rise to the primary tumor [1].”In a new editorial, researchers Ditte S. Christensen and Nicolai J. Birkbak from Aarhus University discuss mechanisms of genomic evolution in metastatic cancer, how therapy can drive it and the implications for developing new treatments. Their editorial paper was published in Oncotarget on March 21, 2023, entitled, “Therapy drives genomic evolution in metastatic cancer.”Full blog - https://www.oncotarget.org/2023/04/14/the-evolution-of-metastatic-cancer-mechanisms-and-drivers/Paper DOI - https://doi.org/10.18632/oncotarget.28379 (PDF)Correspondence to - Nicolai J. Birkbak - nbirkbak@clin.au.dkSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28379Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer evolution, metastatic cancer mutations, treatment-induced mutations, GENIEAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research perspective was published in Oncotarget's Volume 14 on April 14, 2023, entitled, “Cancer prevention with rapamycin.”The mTOR (Target of Rapamycin) pathway is involved in both cancer and aging. Furthermore, common cancers are age-related diseases, and their incidence increases exponentially with age. In his new research perspective, Mikhail V. Blagosklonny, M.D., Ph.D., from Roswell Park Comprehensive Cancer Center discusses rapamycin and other rapalogs and their potential to delay cancer by targeting pre-cancerous cells and slowing down organismal aging.“Rapamycin (sirolimus) and other rapalogs (everolimus) are anti-cancer and anti-aging drugs, which delay cancer by directly targeting pre-cancerous cells and, indirectly, by slowing down organism aging.”Cancer is an age-related disease and, figuratively, by slowing down time (and aging), rapamycin may delay cancer. In several dozen murine models, rapamycin robustly and reproducibly prevents cancer. Rapamycin slows cell proliferation and tumor progression, thus delaying the onset of cancer in carcinogen-treated, genetically cancer-prone and normal mice. Data on the use of rapamycin and everolimus in organ-transplant patients are consistent with their cancer-preventive effects. Treatment with rapamycin was proposed to prevent lung cancer in smokers and former smokers. Clinical trials in high-risk populations are warranted.“Currently, an increasing number of healthy people use rapamycin off-label to slow down aging. Perhaps in ten or twenty years from now, data will accumulate for retrospective analysis of cancer-prevention with rapamycin in humans.”DOI: https://doi.org/10.18632/oncotarget.28410 Correspondence to: Mikhail V. Blagosklonny - Blagosklonny@oncotarget.com, Blagosklonny@rapalogs.com Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28410Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - chemoprevention, lung, rapamycin, aging, cancerAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research paper was published in Oncotarget's Volume 14 on April 10, 2023, entitled, “A phase I trial of riluzole and sorafenib in patients with advanced solid tumors: CTEP #8850.”Overexpression of metabotropic glutamate receptor 1 (GRM1) has been implicated in the pathogenesis of multiple cancers. Riluzole, an inhibitor of glutamate release, showed synergistic antitumor activity in combination with the multi-kinase inhibitor sorafenib in preclinical models.In a new phase I trial, researchers Kristen R. Spencer, Daniella E. Portal, Joseph Aisner, Mark N. Stein, Jyoti Malhotra, Weichung Shih, Nancy Chan, Ann W. Silk, Shridar Ganesan, Susan Goodin, Murugesan Gounder, Hongxia Lin, Jiadong Li, Robert Cerchio, Christina Marinaro, Suzie Chen, and Janice M. Mehnert from Rutgers University, Dana-Farber Cancer Institute, and the Perlmutter Cancer Center of NYU Langone Health identified the toxicity profile, dose-limiting toxicities, maximum tolerated dose (MTD), and pharmacokinetic and pharmacodynamic properties of riluzole combined with sorafenib in patients with advanced cancers.“Riluzole functions as an inhibitor of GRM1 signaling through antagonism of glutamate release, and sorafenib is a multi-kinase inhibitor targeting both the MAPK and PI3K/AKT pathways through the inhibition of RAF1, ARAF and, to a lesser extent BRAF, as well as a set of tyrosine kinases including VEGFR. Our phase I study determined the tolerable dose of this combination and investigated its biologic effects.”Patients with refractory solid tumors were enrolled utilizing a 3+3 dose-escalation design. Riluzole was given at 100 mg PO BID in combination with sorafenib, beginning at 200 mg PO daily and escalating in 200 mg increments per level in 28-day cycles. Restaging evaluations were performed every 2 cycles. In total, 35 patients were enrolled over 4 dose levels. The MTD was declared at dose level 3 (riluzole: 100 mg PO BID; sorafenib: 400 mg AM/200 mg PM). Pharmacokinetic analyses did not reveal definitive evidence of drug-drug interactions. Consistent decreases in phospho-forms of ERK and AKT in tumor tissue analyses with accompanying decrease in GRM1 expression and increase in pro-apoptotic BIM suggest target engagement by the combination. Best responses included a partial response in 1 (2.9%) patient with pancreatic acinar cell carcinoma with a KANK4-RAF1 fusion, and stable disease in 11 (36%) patients.“Combination therapy with riluzole and sorafenib was safe and tolerable in patients with advanced solid tumors. The partial response in a patient with a RAF1 fusion suggests that further exploration in a genomically selected cohort may be warranted.”DOI: https://doi.org/10.18632/oncotarget.28403 Correspondence to: Janice M. Mehnert - Janice.Mehnert@nyulangone.org Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28403Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - GRM1, riluzole, sorafenib, phase I, clinical trialAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/MEDIA@IMPACTJOURNALS.COM
A new review paper was published in Oncotarget's Volume 14 on March 31, 2023, entitled, “Crosstalk between triple negative breast cancer and microenvironment.”Although many advances have been made in the treatment of breast cancer, for triple negative breast cancer (TNBC) these therapies have not significantly increased overall survival. Tumor microenvironment (TME) plays an essential role to develop and control TNBC progression. Many preclinical and clinical studies are ongoing to treat patients with TNBC disease, but effective therapies are currently not available. In their new review, researchers Karly Smrekar, Artem Belyakov and Kideok Jin from Albany College of Pharmacy and Health Science discuss recent progress in our understanding of TNBC, advancements in defining mechanisms of TNBC therapies and potential therapeutic strategies to overcome TNBC.“Technological advancements such as genomics and epigenomics have provided us with vast insight about the complexity of breast cancer. However, one thing has remained the same, the need for the evaluation of three markers. These three markers; the expression of estrogen, progesterone, and HER2, are all molecular targets for treatment regimens, and are relied on by clinicians [1]. Chemotherapy is the staple treatment for TNBC patients. However, they lack the expression of three key therapeutic markers. The lack of therapeutic markers leads to poorer outcomes in TNBC.”DOI: https://doi.org/10.18632/oncotarget.28397 Correspondence to: Kideok Jin - kideok.jin@acphs.edu Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28397Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - triple negative breast cancer, tumor microenvironment, current therapyAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new editorial perspective was published in Oncotarget's Volume 14 on March 21, 2023, entitled, “Cancer-associated fibroblasts: challenges and opportunities.”Cancer-associated fibroblasts (CAFs) are a type of cell that plays a key role in the tumor microenvironment. While these cells have been extensively studied, their precise role in cancer development and progression is still not fully understood. In this new editorial perspective, researchers Hossein Tavana and Gary D. Luker from The University of Akron and the University of Michigan provide a comprehensive overview of CAFs, including the origins, characteristics, heterogeneity, and functions of CAFs, as well as CAFs in the detection and treatment of cancer.The authors suggest that a deeper understanding of cancer-associated fibroblasts is crucial for the development of effective cancer therapies. They note that these cells are involved in a variety of important processes, including tumor growth, angiogenesis and immune evasion. However, targeting cancer-associated fibroblasts has proven to be a challenging task, in part because of their complex and multifaceted nature.Despite these challenges, the researchers are optimistic about the future of research into CAFs. They note a number of studies targeting cancer-associated fibroblasts in emerging therapies. The authors conclude by emphasizing that a deeper understanding of cancer-associated fibroblasts and the tumor microenvironment could ultimately lead to the development of personalized therapies that are tailored to the unique characteristics of each patient's cancer.“Delineating cross-talk of CAFs with cancer cells and other stromal cells, uncovering the role of CAFs in resistance to chemotherapies and immunotherapies, addressing challenges associated with CAFs heterogeneity to develop CAFs subtype-targeted therapies in the context of specific tumor types, and addressing the potential toxicity of such therapies especially when combined with other treatments will expedite the ongoing efforts for the translation of therapies against CAFs.”Editorial perspective: DOI: https://doi.org/10.18632/oncotarget.28385 Correspondence to: Hossein Tavana - tavana@uakron.edu Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - fibroblasts, cancer-associated fibroblasts, tumor microenvironment, therapeutic targetingAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new editorial paper was published in Oncotarget's Volume 14 on March 21, 2023, entitled, “Impact of cortactin in cancer progression on Wnt5a/ROR1 signaling pathway.”In this editorial, researchers Kamrul Hasan and Thomas J. Kipps from the University of California discuss cortactin—an intracellular cytoskeletal protein that can undergo tyrosine phosphorylation upon external stimulation and promote polymerization and the assembly of the actin filament that is required for cell migration. Upon stimulation, cortactin binds and activates actin related protein Arp2/3 complex, a de novo actin nucleator that can induce F (filamentous)-actin polymerization [1, 2]. Cortactin (also known as EMS1 or CTTN) is expressed broadly in a variety of cancers, for which it plays an apparent role in cellular protrusions, which include lamellipodia and filopodia formation to promote migration and metastasis. Moreover, cortactin is expressed in (i) primary chronic lymphocytic leukemia (CLL) and primary breast-cancer cells, (ii) at least 15% of metastatic breast carcinomas, and (iii) CLL or breast-cancer cell-lines [3, 4]. In structure, cortactin contains a SH3 domain that allows it to bind characteristic motifs (-P-X-X-P-), which can be found in the proline-rich-domains (PRD) of other proteins, including receptor-tyrosine-kinase-like orphan receptor 1 (ROR1) [1, 3, 4]. “We have found (as have other investigators) that ROR1 is expressed by a variety of human cancers, which include CLL and breast cancer, suggesting that ROR1 may play a role in cancer pathogenesis [3–5].”Editorial paper: DOI: https://doi.org/10.18632/oncotarget.28386Correspondence to: Thomas J. Kipps - tkipps@ucsd.edu Keywords: cortactin, Wnt5a, ROR1, migration, metastasisSubscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/About OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Impact Journals (Oncotarget's publisher) will be participating as an exhibitor at the American Association for Cancer Research (AACR) Annual Meeting 2023 from April 14-19 at the Orange County Convention Center in Orlando, Florida. This year, the AACR meeting theme is: “Advancing the Frontiers of Cancer Science and Medicine.”Impact Journals publishes scholarly journals in the biomedical sciences with a focus on all areas of cancer and aging research. Oncotarget is one of the most prominent journals published by Impact Journals. Oncotarget is indexed/archived on MEDLINE, PMC and PubMed.Visit booth No. 2642 at the AACR Annual Meeting 2023 to connect with members of the Oncotarget team.Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - cancer, cancer research, aacr, aacr23, aacr2023, annual meeting, meeting, conference, press, press release, announcementAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Listen to a blog summary of an editorial in Volume 14, entitled, “Proof-of-principle: targeted childhood leukemia prevention.” ___________________________________________Childhood leukemia is a devastating disease that affects thousands of children every year. Despite significant advancements in the field of pediatric oncology, childhood leukemia remains a major cause of morbidity and mortality in children, with B-cell acute lymphoblastic leukemia (B-ALL) being the most common form. Some cases of childhood B-ALL arise from congenital mutations that lead to a silent population of pre-leukemic cells. These cells at some point are triggered by a catalyst (possibly by delayed exposure to a common infection), acquire additional genetic mutations and ultimately develop into B-ALL. However, researchers have yet to fully understand how to target these pre-leukemic cells to prevent B-ALL.In a new editorial paper, researchers César Cobaleda, Manuel Ramírez-Orellana, Carolina Vicente-Dueñas, Andreas Weiss, Kim E. Nichols, and Isidro Sánchez-García from Universidad Autónoma de Madrid discuss a novel method of targeting pre-leukemic cells in practice. On March 11, 2023, the team published their editorial in Oncotarget, entitled, “Proof-of-principle: targeted childhood leukemia prevention.” “[…] one would have to find a way to specifically target these preleukemic cells. Recently, a mouse model recapitulating the phenotype of a leukemia-predisposition syndrome has allowed us to carry out a proof-of-principle experiment to achieve this very goal.”Full blog - https://www.oncotarget.org/2023/03/31/targeting-pre-leukemic-cells-new-hope-for-preventing-childhood-b-all/Paper DOI - https://doi.org/10.18632/oncotarget.28371Correspondence to - César Cobaleda - cesar.cobaleda@csic.esSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/deta...Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - leukemia, infection, murine models, genetic susceptibility, preventionAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research paper was published in Oncotarget's Volume 14 on March 24, 2023, entitled, “Downregulation of angulin-1/LSR induces malignancy via upregulation of EGF-dependent claudin-2 and TGF-β-dependent cell metabolism in human lung adenocarcinoma A549 cells.”Abnormal expression of bicellular tight junction claudins, including claudin-2 are observed during carcinogenesis in human lung adenocarcinoma. However, little is known about the role of tricellular tight junction molecule angulin-1/lipolysis-stimulated lipoprotein receptor (LSR). In the present study, researchers Wataru Arai, Takumi Konno, Takayuki Kohno, Yuki Kodera, Mitsuhiro Tsujiwaki, Yuma Shindo, Hirofumi Chiba, Masahiro Miyajima, Yuji Sakuma, Atsushi Watanabe, and Takashi Kojima from Sapporo Medical University School of Medicine examined expression of claudin-2 in the lung adenocarcinoma tissues and found it was higher than in normal lung tissues, while angulin-1/LSR was poorly or faintly expressed. “We investigated how loss of angulin-1/LSR affects the malignancy of lung adenocarcinoma cell line A549 and normal human lung epithelial (HLE) cells.” The researchers found that the EGF receptor tyrosine kinase inhibitor AG1478 prevented the increase of claudin-2 expression induced by EGF in A549 cells. Knockdown of LSR induced expression of claudin-2 at the protein and mRNA levels and AG1478 prevented the upregulation of claudin-2 in A549 cells. Knockdown of LSR induced cell proliferation, cell migration and cell metabolism in A549 cells. Knockdown of claudin-2 inhibited the cell proliferation but did not affect the cell migration or cell metabolism of A549 cells. The TGF-β type I receptor inhibitor EW-7197 prevented the decrease of LSR and claudin-2 induced by TGF-β1 in A549 cells and 2D culture of normal HLE cells. EW-7197 prevented the increase of cell migration and cell metabolism induced by TGF-β1 in A549 cells. EW-7197 prevented the increase of epithelial permeability of FITC-4kD dextran induced by TGF-β1 in 2.5D culture of normal HLE cells. In conclusion, downregulation of angulin-1/LSR induces malignancy via EGF-dependent claudin-2 and TGF-β-dependent cell metabolism in human lung adenocarcinoma.“In conclusion, AG1478 and EW-7197 demonstrated potent in vitro anti-lung adenocarcinoma therapeutic activities via LSR/CLDN-2 and the cell metabolism. The use of both AG1478 and EW-7197 may provide a clinical therapeutic approach for lung adenocarcinoma caused by loss of angulin-1/LSR.”Full research paper: DOI: https://doi.org/10.18632/oncotarget.27728 Correspondence to: Takashi Kojima - ktakashi@sapmed.ac.jp Keywords: angulin-1/LSR, claudin-2, cell metabolism, malignancy, lung adenocarcinomaAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research paper was published in Oncotarget's Volume 14 on March 24, 2023, entitled, “Polyisoprenylated cysteinyl amide inhibitors deplete singly polyisoprenylated monomeric G-proteins in lung and breast cancer cell lines.”Finding effective therapies against cancers driven by mutant and/or overexpressed hyperactive G-proteins remains an area of active research. Polyisoprenylated cysteinyl amide inhibitors (PCAIs) are agents that mimic the essential posttranslational modifications of G-proteins. It is hypothesized that PCAIs work as anticancer agents by disrupting polyisoprenylation-dependent functional interactions of the G-Proteins. In their new study, researchers Nada Tawfeeq, Jassy Mary S. Lazarte, Yonghao Jin, Matthew D. Gregory, and Nazarius S. Lamango from Florida A&M University College of Pharmacy Pharmaceutical Sciences and Imam Abdulrahman bin Faisal University tested this hypothesis by determining the effect of the PCAIs on the levels of RAS and related monomeric G-proteins. “To investigate the hypothesized anticancer mechanisms of the PCAIs through disruption of G-protein function, we checked the effects of the PCAIs on the G-protein levels in lung cancer (A549 and NCI-H1299) and breast cancer (MDA-MB-231 and MDA-MB-468) cell lines.”Following 48 hours of exposure, they found significant decreases in the levels of KRAS, RHOA, RAC1, and CDC42 ranging within 20–66% after NSL-YHJ-2-27 (5 μM) treatment in all four cell lines tested, A549, NCI-H1299, MDA-MB-231, and MDA-MB-468. However, no significant difference was observed on the G-protein, RAB5A. Interestingly, 38 and 44% decreases in the levels of the farnesylated and acylated NRAS were observed in the two breast cancer cell lines, MDA-MB-231, and MDA-MB-468, respectively, while HRAS levels showed a 36% decrease only in MDA-MB-468 cells. Moreover, after PCAIs treatment, migration, and invasion of A549 cells were inhibited by 72 and 70%, respectively while the levels of vinculin and fascin dropped by 33 and 43%, respectively. Their results show that PCAIs deplete the protein levels of some significant G-proteins which are known to be involved in the migration and invasion of cells (i.e., metastasis) such as RAC1, RHOA, and CDC42. These findings implicate the potential role of PCAIs as anticancer agents through their direct interaction with monomeric G-proteins.“The initial findings presented here indicate how PCAIs can be used as potent agents in developing new anticancer therapeutics, therefore, more extensive studies need to be done to elucidate on its potency. Although we cannot conclusively explain the exact mechanism of action of PCAIs on how they affect the levels of some G-proteins yet, but we can say that these PCAIs have the ability to affect the progression of cancer.”Research paper: DOI: https://doi.org/10.18632/oncotarget.28390 Correspondence to: Nazarius S. Lamango - nazarius.lamango@famu.edu Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords: PCAIs, G-proteins, KRAS, RHOA, RAC1About OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research paper was published in Oncotarget's Volume 14 on March 21, 2023, entitled, “Attenuation of cancer proliferation by suppression of glypican-1 and its pleiotropic effects in neoplastic behavior.”Glypicans (GPC1-6) are associated with tumorigenic processes and their involvement in neoplastic behavior has been discussed in different cancer types. In this recent cancer-wide GPC expression study, researchers Fang Cheng, Victor Chérouvrier Hansson, Grigorios Georgolopoulos, and Katrin Mani from Lund University and Genevia Technologies used clinical cancer patient data in The Cancer Genome Atlas to reveal net upregulation of GPC1 and GPC2 in primary solid tumors. On the other hand, GPC3, GPC5 and GPC6 displayed lowered expression patterns compared to normal tissues. “[...] we identify and propose a mechanism where GPC1 interacts with extracellular matrix mediating signal transduction by mitogenic molecules involving TGF-β and p38 MAPK.”Focusing on GPC1, the researchers conducted survival analyses of the clinical cancer patient data that revealed a statistically significant correlation between high expression of GPC1 and poor prognosis in 10 particular cancer types: bladder urothelial carcinoma, brain lower grade glioma, liver hepatocellular carcinoma, colon adenocarcinoma, kidney renal clear cell carcinoma, lung adenocarcinoma, mesothelioma, ovarian serous cystadenocarcinoma, uterine corpus endometrial carcinoma, and uveal melanoma. In vitro studies targeting GPC1 expression by CRISPR/Cas9 or siRNA or treatment with an anti-GPC1 antibody resulted in attenuation of proliferation of cancer cells from bladder carcinoma, glioma and hepatocellular carcinoma patients (T24, U87 and HepG2 cells). Further, GPC1 overexpression exhibited a significant and negative correlation between GPC1 expression and proliferation of T24 cells. Their attempt to reveal the mechanism through which downregulation of GPC1 leads to attenuation of tumor growth using systematic Ingenuity Pathway Analysis indicated that suppression of GPC1 results in ECM-mediated inhibition of specific pro-cancer signaling pathways involving TGF-β and p38 MAPK. The team also identified differential expression and pleiotropic effects of GPCs in specific cancer types. This emphasizes their potential as novel diagnostic tools and prognostic factors, and open doors for future GPC targeted therapy.“It is plausible to measure circulating GPCs in serum, plasma or urine using a variety of methods including ELISA, urine cell sediments or exosome isolation [13, 24]. Further, detection and quantification of GPC1 by histopathological and immunohistochemical methods in tumor biopsies could be a new way to predict the biological outcome. The results of this investigation would also emphasize the potential of GPCs as novel tumor antigens, and open for GPC targeted immunotherapy. GPC targeted immunotherapy would be of high value, especially as we move into an era of precision and personalized cancer therapy.”DOI: https://doi.org/10.18632/oncotarget.28388 Correspondence to: Katrin Mani - katrin.mani@med.lu.se Keywords: Glypican-1, TCGA, bladder carcinoma, hepatocellular carcinoma, gliomaAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetMEDIA@IMPACTJOURNALS.COM
A new editorial paper was published in Oncotarget's Volume 14 on February 11, 2023, entitled, “Unlocking the potential of molecular-driven stratification for osteosarcoma treatment and prognosis.”Over the last 40 years, the complex genetic landscape, the heterogeneity of the microenvironment and the cell plasticity of Osteosarcoma (OSA) tumors have delayed the therapeutic and prognostic stratification of patients and the introduction of new efficient treatments. As a direct consequence, the vast majority of trials still don’t benefit from a selection of OSA patient-based on molecular evidence before drug administration. This lack of stratification leads to difficult interpretation of outcome, especially with targeted agents such as multikinase inhibitors or anti-osteoclastic drugs.“Meanwhile, fortunately, the accumulation of numerous sparse but converging observations from many research and clinical teams have progressively drawn a portrait of the resistant osteosarcoma that’s paved the way to new translational discoveries.”In their new editorial, researchers Gaël Moquin-Beaudry, Maria Eugenia Marques da Costa, Nathalie Gaspar, and Antonin Marchais from Université Paris-Saclay discussed their recent study using unsupervised machine learning algorithms to classify OSA at diagnosis based on gene expression modules functionally enriched for immune microenvironment and tumor phenotypic traits.“Recently, several important studies have described OSA molecularly at an unprecedent[ed] level of detail taking advantage of multiomics approaches and artificial intelligence [1–3].”Read the full editorial: DOI: https://doi.org/10.18632/oncotarget.28364 Correspondence to: Antonin Marchais - ANTONIN.MARCHAIS@gustaveroussy.fr Keywords: multiomics, osteosarcoma, bone sarcoma,stratificationAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Blog summary of an editorial perspective published in Oncotarget on entitled, “Leakage? or Secretion? unconventional protein secretion in cancer.”________________________________________Conventional protein secretion is fairly well understood in this day and age. Proteins that are secreted through the classical, secretory vesicle-related pathway contain a signal peptide that guides them to the endoplasmic reticulum (ER), where they are further processed and transported to the Golgi apparatus. From there, the Golgi apparatus modifies, sorts and packages proteins for transport to their final destinations within the cell or for secretion outside of the cell. However, in recent years, it has become clear that not all secreted proteins follow this conventional pathway. Instead, some proteins are secreted through unconventional pathways that do not require a signal peptide or the involvement of the ER or Golgi apparatus. In a recent editorial perspective published in Oncotarget on February 20, 2023, “Leakage? or Secretion? unconventional protein secretion in cancer,” researchers Kohji Yamada and Kiyotsugu Yoshida from The Jikei University School of Medicine in Tokyo, Japan, discuss unconventional protein secretion (UPS) and its significance in the progression of cancer. “In contrast, the secretion of proteins that do not code for signal peptides may occur via two or more mechanisms, often collectively referred to as unconventional protein secretion (UPS).”Full blog - https://www.oncotarget.org/2023/03/16/unconventional-protein-secretion-ups-in-cancer/DOI - https://doi.org/10.18632/oncotarget.28368 (PDF Download)Correspondence to - Kohji Yamada - kyamada@jikei.ac.jp, and Kiyotsugu Yoshida - kyoshida@jikei.ac.jpSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28368Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/Keywords - unconventional protein secretion, cancer, endoplasmic reticulumAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research paper was published in Oncotarget's Volume 14 on March 11, 2023, entitled, “Genomic landscape of metastatic breast cancer (MBC) patients with methylthioadenosine phosphorylase (MTAP) loss.”Homozygous deletion of methylthioadenosine phosphorylase (MTAP) upregulates de novo synthesis of purine (DNSP) and increases the proliferation of neoplastic cells. This increases the sensitivity of breast cancer cells to DNSP inhibitors such as methotrexate, L-alanosine and pemetrexed. In their recent study, Maroun Bou Zerdan, Prashanth Ashok Kumar, Elio Haroun, Nimisha Srivastava, Jeffrey Ross, and Abirami Sivapiragasam from SUNY Upstate Medical University and Foundation Medicine, Inc. analyzed 7,301 metastatic breast cancer (MBC) patients that underwent hybrid-capture based comprehensive genomic profiling (CGP). “We provide one of the first large analyses of the spectrum of GA [genomic alterations] occurring in MTAP deleted MBC with the hope that this would enable identifying potential therapeutic agents in the future.”Tumor mutational burden (TMB) was determined on up to 1.1 Mb of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. Tumor cell PD-L1 expression was determined by IHC (Dako 22C3). 208 (2.84%) of MBC featured MTAP loss. MTAP loss patients were younger (p = 0.002) and were more frequently ER− (30% vs. 50%; p < 0.0001), triple negative (TNBC) (47% vs. 27%; p < 0.0001) and less frequently HER2+ (2% vs. 8%; p = 0.0001) than MTAP intact MBC. Lobular histology and CDH1 mutations were more frequent in MTAP intact (14%) than MTAP loss MBC (p < 0.0001). CDKN2A (100%) and CDKN2B (97%) loss (9p21 co-deletion) were significantly associated with MTAP loss (p < 0.0001). Likely associated with the increased TNBC cases, BRCA1 mutation was also more frequent in MTAP loss MBC (10% vs. 4%; p < 0.0001). As for immune checkpoint inhibitors biomarkers, higher TMB >20 mut/Mb levels in the MTAP intact MBC (p < 0.0001) and higher PD-L1 low expression (1–49% TPS) in the MTAP loss MTAP (p = 0.002) were observed.“MTAP loss in MBC has distinct clinical features with genomic alterations (GA) affecting both targeted and immunotherapies. Further efforts are necessary to identify alternative means of targeting PRMT5 and MTA2 in MTAP-ve cancers to benefit from the high-MTA environment of MTAP-deficient cancers.”Read the full research paper: DOI: https://doi.org/10.18632/oncotarget.28376 Correspondence to: Abirami Sivapiragasam - sivapira@upstate.edu Keywords: breast cancer, metastatic, MTAP lossAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new review paper was published in Oncotarget's Volume 14 on March 11, 2023, entitled, “Selective protection of normal cells from chemotherapy, while killing drug-resistant cancer cells.”Cancer therapy is limited by toxicity in normal cells and drug-resistance in cancer cells. In his latest review, Mikhail V. Blagosklonny, M.D., Ph.D., from Roswell Park Comprehensive Cancer Center discusses the theory that cancer resistance to certain therapies can be exploited for protection of normal cells—simultaneously enabling the selective killing of resistant cancer cells by using antagonistic drug combinations, which include cytotoxic and protective drugs. “No cancer cell, no matter how resistant it is, can survive chemotherapy in a cell culture. In the organism, however, therapy of cancer is limited by killing or damaging normal cells. Selective protection of normal cells from chemotherapy would increase the therapeutic window, improving the therapeutic outcome. Needless to say, reduction of side effects and better quality of life are very important for a cancer patient.”Depending on the mechanisms of drug-resistance in cancer cells, the protection of normal cells can be achieved with inhibitors of CDK4/6, caspases, Mdm2, mTOR, and mitogenic kinases. When normal cells are protected, the selectivity and potency of multi-drug combinations can be further enhanced by adding synergistic drugs, in theory, eliminating the deadliest cancer clones with minimal side effects. “I also discuss how the recent success of Trilaciclib may foster similar approaches into clinical practice, how to mitigate systemic side effects of chemotherapy in patients with brain tumors and how to ensure that protective drugs would only protect normal cells (not cancer cells) in a particular patient.”Read the full review: DOI: https://doi.org/10.18632/oncotarget.28382 Correspondence to: Mikhail V. Blagosklonny - Blagosklonny@oncotarget.com, Blagosklonny@rapalogs.com Keywords: oncology, resistance, cyclotherapy, trilaciclib, rapamycinAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new editorial paper was published in Oncotarget's Volume 14 on February 25, 2023, entitled, “Mitochondria engage the integrated stress response to promote tumor growth.”In this new editorial, researchers Dillon P. Boulton and M. Cecilia Caino from the University of Colorado School of Medicine discussed prostate cancer (PCa)—the most diagnosed and second deadliest cancer among men in the United States, with an estimated 268,490 new cases and 34,500 deaths in 2022 (ACS Cancer Facts and Figures 2022). “While the prognosis for men with early-stage disease remains extremely favorable (>99% 5-year overall survival, OS), men diagnosed with metastatic PCa have a 30% 5-year OS, clearly demonstrating a need for therapeutic options for these patients (ACS Cancer Facts and Figures 2022).”Due to a strong reliance on androgens to drive PCa, first and second courses of therapy involve androgen deprivation therapy or targeting the androgen receptor directly in combination with several other cytotoxic agents [1–3]. Unfortunately, some tumors develop resistance to these androgen axis therapies and progress to castrate resistant and metastatic PCa, which drives the majority of PCa deaths. This underscores a strong need to identify and characterize actionable targets within these tumors. Of interest, mitochondria are emerging as critical organelles that promote tumorigenesis and metastasis.“Along this line, we have recently described a novel signaling pathway where mitochondria promote castrate resistant metastatic PCa growth by acting as a signaling platform to facilitate efficient stress signaling [11]. This pathway is centered around mitochondrial Rho GTPase 2 (MIRO2), an outer-mitochondrial membrane protein in the Ras superfamily of GTPases [12, 13].”Full editorial: DOI: https://doi.org/10.18632/oncotarget.28372 Correspondence to: M. Cecilia Caino - Cecilia.caino@cuanschutz.edu Keywords: mitochondria, prostate cancer, integrated stress responseAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new review paper was published in Oncotarget's Volume 14 on February 25, 2023, entitled, “What is hemoglobin, albumin, lymphocyte, platelet (HALP) score? A comprehensive literature review of HALP’s prognostic ability in different cancer types.”Since its inception, the Hemoglobin, Albumin, Lymphocyte, Platelet (HALP) Score has gained attention as a new prognostic biomarker to predict several clinical outcomes in a multitude of cancers. “HALP is a novel immune-nutritional marker that integrates several routinely collected indicators of immune status, such as the platelet and lymphocyte count, nutritional status, such as albumin, and hemoglobin, a marker for anemia.”In this new review, researchers Christian Mark Farag, Ryan Antar, Sinan Akosman, Matthew Ng, and Michael J. Whalen from George Washington University School of Medicine searched PubMed for articles on HALP, from the first paper in 2015 through September 2022. Their search yielded a total of 32 studies that evaluated HALP's association with various cancers, including Gastric, Colorectal, Bladder, Prostate, Kidney, Esophageal, Pharyngeal, Lung, Breast, Cervical cancers, and others. “This review highlights the collective association HALP has with demographic factors such as age and sex in addition to TNM staging, grade, and tumor size.”Furthermore, this review summarizes HALP's prognostic ability to predict overall survival, progression-free survival and recurrence-free survival, among other outcomes. In some studies, HALP has also been able to predict response to immunotherapy and chemotherapy. Their review article also aims to serve as a comprehensive and encyclopedic report on the literature that has evaluated HALP as a biomarker in various cancers, highlighting the heterogeneity surrounding HALP's utilization. “Because HALP requires only a complete blood count and albumin - already routinely collected for cancer patients - HALP shows potential as a cost-effective biomarker to aid clinicians in improving outcomes for immuno-nutritionally deficient patients.”Full review: DOI: https://doi.org/10.18632/oncotarget.28367 Correspondence to: Christian Mark Farag - cmfarag@gwu.edu Keywords: HALP score, biomarker, prognosis, cancer, survivalAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new editorial paper was published in Oncotarget's Volume 14 on February 11, 2023, entitled, “Unveiling the non-canonical functions of EZH2 in prostate cancer.”Prostate cancer (PCa) is ranked as the second leading cause of cancer-related death among American men excluding skin cancer. In this new editorial, researchers Yang Yi, Yanqiang Li, Kaifu Chen, and Qi Cao from Northwestern University’s Feinberg School of Medicine discuss a well-known oncogenic driver in PCa: enhancer of zeste homolog 2 (EZH2)—canonically known for the functions as the catalytic subunit of Polycomb Repressive Complex 2 (PRC2) that deposes histone H3 lysine 27 mono, di-, and tri-methylation (H3K27me1-3) and represses transcription. “Although the oncogenic role of EZH2 mainly relies on its enzymatic activity and the PRC2, accumulating evidence suggests that targeting the lysine methyltransferase activity of EZH2 alone is ineffective in treating EZH2-dependent malignancies including PCa [4, 5].”Hence, deeply investigating the multifaceted tumorigenic functions of EZH2 will shed new light on understanding the etiology of PCa. It is noteworthy that two recent studies published in Nature Cell Biology and Oncogene by Yi et al. described previously unrecognized roles of EZH2 in regulation of translation and coactivation of transcription, respectively. In both cases, EZH2 exerts oncogenic functions independently of PRC2 and H3K27me3 to promote tumorigenesis and aggressiveness in PCa.“In summary, both articles by Yi et al. emphasized the significance of non-canonical functions of EZH2 during PCa development, which may provide novel insights into the advancement of EZH2-targeting strategies to treat PCa patients. In fact, a new wave has been ushed for the discovery of EZH2 inhibitors to eliminate both the catalytic and non-catalytic activities of EZH2 [12–14]. Will these newly developed EZH2 degraders be successfully applied in PCa therapy? Will additional noncanonical functions of EZH2 be characterized in the PCa model? Let’s eagerly wait and see.”Full editorial: DOI: https://doi.org/10.18632/oncotarget.28357 Correspondence to: Qi Cao - qi.cao@northwestern.edu Keywords: EZH2, prostate cancer, FBL, CDCA8, E2F1Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28357Keywords - EZH2, prostate cancer, FBL, CDCA8, E2F1About OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Blog summary of an editorial published in Volume 14 of Oncotarget, entitled, “The role of Kras and canonical Wnt pathways for tumorigenesis of extrahepatic biliary system.”____________________________________________________The extrahepatic biliary system is a network of tubes and ducts that carry bile from the liver to the small intestine, where it helps digest fats. Biliary tract cancers, including gallbladder cancer and cholangiocarcinoma, are rare but aggressive cancers that arise from this system. Understanding the molecular mechanisms that drive these cancers is crucial for developing effective therapies.“Despite advances in diagnosis and therapy, 5-year survival rate of biliary cancer is only 5% to 15% [7, 8].”In a new editorial, researchers Munemasa Nagao, Akihisa Fukuda and Hiroshi Seno from Kyoto University Graduate School of Medicine discuss the latest research on the role of Kras and the canonical Wnt pathway in the development of biliary tract cancers. On January 26, 2023, their paper was published in Oncotarget’s Volume 14, entitled, “The role of Kras and canonical Wnt pathways for tumorigenesis of extrahepatic biliary system.”Full blog - https://www.oncotarget.org/2023/03/01/the-role-of-kras-and-canonical-wnt-pathways-in-biliary-tract-cancers/DOI - https://doi.org/10.18632/oncotarget.28349 (PDF Download)Correspondence to - Akihisa Fukuda - fukuda26@kuhp.kyoto-u.ac.jpSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28349Keywords - ICPN, BilIN, biliary cancer, Kras, WntAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research perspective was published in Oncotarget's Volume 14 on February 7, 2023, entitled, “WNT-pathway medulloblastoma: what constitutes low-risk and how low can one go?”Novel biological insights have established that medulloblastoma is a heterogenous disease comprising four broad molecular subgroups - WNT, SHH, Group 3, and Group 4 respectively, resulting in the incorporation of molecular/genetic information in 5th edition of WHO classification and contemporary risk-stratification. Concerns regarding therapy-related late toxicity in long-term survivors have led to systematic attempts at treatment de-intensification in good-risk medulloblastoma. Given the excellent survival (>90%) of WNT-pathway medulloblastoma, prospective clinical trials have focused on optimization of therapy to balance survival versus quality of survival. The currently accepted definition of low-risk WNT-pathway medulloblastoma includes children <16 years of age with residual tumour <1.5 cm2 and no evidence of metastases. This systematically excludes adolescents and young adults who have been perceived to have worse outcomes. In a previous study, researchers Shakthivel Mani, Abhishek Chatterjee, Archya Dasgupta, Neelam Shirsat, Sridhar Epari, Girish Chinnaswamy, and Tejpal Gupta from Homi Bhabha National Institute (HBNI) in Mumbai, India, reported long-term survival of an adolescent and young adult cohort that was largely comparable to childhood medulloblastoma. In their current research perspective, the researchers now report on molecularly characterized WNT-subgroup patients treated between 2004–2020 with risk-stratified multi-modality therapy to identify differences between childhood (<15 years) versus adolescent and young adults (>15 years). Despite modest differences in disease status at presentation and treatment modality, there were no significant differences in patterns of failure or survival between childhood versus adolescent and young adult WNT-pathway medulloblastoma. Two de-intensification trials in low-risk WNT-pathway medulloblastoma – first testing omission of upfront craniospinal irradiation and second a primary chemotherapy approach after surgery – had to be terminated prematurely due to unacceptably high relapse rates suggesting that craniospinal irradiation remains an integral component of treatment. The presence of TP53 mutations and OTX2 gains have recently been reported as independent negative prognostic factors in a multi-institutional cohort of WNT-pathway medulloblastoma, raising questions on eligibility of such patients for de-escalation trials. “Concerns regarding therapy-related late toxicity have prompted systematic attempts at treatment de-intensification in good-risk MB over the last four decades. However, results of prior studies should be used to inform and guide controlled de-intensification of therapy even in low-risk and favourable biology disease. The definition of low-risk WNT-MB may need to be further refined in light of recent clinical data and newer biological information.”DOI: https://doi.org/10.18632/oncotarget.28360 Correspondence to: Tejpal Gupta - tejpalgupta@rediffmail.com Keywords: de-intensification, medulloblastoma, molecular, survival, toxicitySign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28360Keywords - de-intensification, medulloblastoma, molecular, survival, toxicityAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.Visit https://www.oncotarget.com
A new research paper was published in Oncotarget's Volume 14 on February 11, 2023, entitled, “Oncogenic driver FGFR3-TACC3 requires five coiled-coil heptads for activation and disulfide bond formation for stability.”FGFR3-TACC3 represents an oncogenic fusion protein frequently identified in glioblastoma, lung cancer, bladder cancer, oral cancer, head and neck squamous cell carcinoma, gallbladder cancer, and cervical cancer. Various exon breakpoints of FGFR3-TACC3 have been identified in cancers. In this recent study, researchers Clark G. Wang, Malalage N. Peiris, April N. Meyer, Katelyn N. Nelson, and Daniel J. Donoghue from University of California San Diego analyzed these FGFR3-TACC3 exon breakpoints to determine the minimum contribution of TACC3 for activation of the FGFR3-TACC3 fusion protein. “In this work, we characterize the signaling, transforming abilities, and post-translational modifications of FGFR3-TACC3 fusion proteins arising from different exonic breakpoints to determine the requirements for dimerization and constitutive activation of the fusion protein.”While TACC3 exons 11 and 12 are dispensable for activity, the researchers’ results show that FGFR3-TACC3 requires exons 13-16 for biological activity. A detailed analysis of exon 13, which consists of 8 heptads forming a coiled coil, further defined the minimal region for biological activity as consisting of 5 heptads from exon 13, in addition to exons 14-16. These conclusions were supported by transformation assays of biological activity, examination of MAPK pathway activation, analysis of disulfide-bonded FGFR3-TACC3, and by examination of the Endoglycosidase H-resistant portion of FGFR3-TACC3. These results demonstrate that clinically identified FGFR3-TACC3 fusion proteins differ in their biological activity, depending upon the specific breakpoint. This study further suggests the TACC3 dimerization domain of FGFR3-TACC3 as a novel target in treating FGFR translocation driven cancers.“Taken together, these results provide a better understanding of the mechanism for activation of FGFR3-TACC3 and narrow the scope of targeting TACC3 to create effective dimerization disruption-based therapies for treating patients with FGFR3-TACC3 driven tumors.”DOI: https://doi.org/10.18632/oncotarget.28359 Correspondence to: Daniel J. Donoghue - ddonoghue@ucsd.eduKeywords: oncogenic fusion protein, chromosomal translocation, glioblastoma, FGFR3-TACC3, coiled-coilAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/@OncotargetJournalLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Crossref is a non-profit organization that logs and updates citations for scientific publications. Each month, Crossref identifies a list of the most popular Oncotarget papers based on the number of times a DOI is successfully resolved. Below are Crossref’s Top 10 Oncotarget DOIs in 2022.#10: Cell fusion as a link between the SARS-CoV-2 spike protein, COVID-19 complications, and vaccine side effectsDOI: https://doi.org/10.18632/oncotarget.28088Author: Yuri Lazebnik#9: A Jurkat 76 based triple parameter reporter system to evaluate TCR functions and adoptive T cell strategiesDOI: https://doi.org/10.18632/oncotarget.24807Authors: Sandra Rosskopf, Judith Leitner, Wolfgang Paster, Laura T. Morton, Renate S. Hagedoorn, Peter Steinberger, and Mirjam H.M. Heemskerk#8: IL-37 suppresses hepatocellular carcinoma growth by converting pSmad3 signaling from JNK/pSmad3L/c-Myc oncogenic signaling to pSmad3C/P21 tumor-suppressive signalingDOI: https://doi.org/10.18632/oncotarget.13196Authors: Rui Liu, Chengyong Tang, Ai Shen, Huating Luo, Xufu Wei, Daofeng Zheng, Chao Sun, Zhongtang Li, Di Zhu, Tingting Li, and Zhongjun Wu#7: Apatinib-based targeted therapy against pulmonary sarcomatoid carcinoma: a case report and literature reviewDOI: https://doi.org/10.18632/oncotarget.25989Authors: Xiaofeng Li, Yueming He, Jinfeng Zhu, Hongxia Pang, Yongwei Lin, and Jinyang Zheng#6: Treasures from trash in cancer researchDOI: https://doi.org/10.18632/oncotarget.28308Authors: Fabiano Cordeiro Moreira, Dionison Pereira Sarquis, Jorge Estefano Santana de Souza, Daniel de Souza Avelar, Taíssa Maria Thomaz Araújo, André Salim Khayat, Sidney Emanuel Batista dos Santos, and Paulo Pimentel de Assumpção#5: Real-world survival analysis by tumor mutational burden in non-small cell lung cancer: a multisite U.S. studyDOI: https://doi.org/10.18632/oncotarget.28178Authors: Connor Willis, Hillevi Bauer, Trang H. Au, Jyothi Menon, Sudhir Unni, Dao Tran, Zachary Rivers, Wallace Akerley, Matthew B. Schabath, Firas Badin, Ashley Sekhon, Malini Patel, Bing Xia, Beth Gustafson, John L. Villano, John-Michael Thomas, Solomon J. Lubinga, Michael A. Cantrell, Diana Brixner, and David Stenehjem#4: Continuous treatment with abemaciclib leads to sustained and efficient inhibition of breast cancer cell proliferationDOI: https://doi.org/10.18632/oncotarget.28249Authors: Raquel Torres-Guzmán, Maria Patricia Ganado, Cecilia Mur, Carlos Marugan, Carmen Baquero, Yanzhu Yang, Yi Zeng, Huimin Bian, Jian Du, Alfonso de Dios, Oscar Puig, and María José Lallena#3: Increased gut permeability in cancer cachexia: mechanisms and clinical relevanceDOI: https://doi.org/10.18632/oncotarget.24804Authors: Laure B. Bindels, Audrey M. Neyrinck, Audrey Loumaye, Emilie Catry, Hannah Walgrave, Claire Cherbuy, Sophie Leclercq, Matthias Van Hul, Hubert Plovier, Barbara Pachikian, Luis G. Bermúdez-Humarán, Philippe Langella, Patrice D. Cani, Jean-Paul Thissen, and Nathalie M. Delzenne#2: Inflammatory responses and inflammation-associated diseases in organsDOI: https://doi.org/10.18632/oncotarget.23208Authors: Linlin Chen, Huidan Deng, Hengmin Cui, Jing Fang, Zhicai Zuo, Junliang Deng, Yinglun Li, Xun Wang, and Ling Zhao#1: Proteomic profiling of skeletal and cardiac muscle in cancer cachexia: alterations in sarcomeric and mitochondrial protein expressionDOI: https://doi.org/10.18632/oncotarget.25146Authors: Angie M. Y. Shum, Anne Poljak, Nicholas L. Bentley, Nigel Turner, Timothy C. Tan, and Patsie Polly_______________________________About OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com
PRESS RELEASE - A new research paper was published in Oncotarget's Volume 14 on February 7, 2023, entitled, “The ‘extreme phenotype approach’ applied to male breast cancer allows the identification of rare variants of ATR as potential breast cancer susceptibility alleles.”In oncogenetics, some patients could be considered as “extreme phenotypes”, such as those with very early onset presentation or multiple primary malignancies, unusually high numbers of cancers of the same spectrum or rare cancer types in the same parental branch. For these cases, a genetic predisposition is very likely, but classical candidate gene panel analyses often, and frustratingly, remains negative. In this new study, researchers Martin Chevarin, Diana Alcantara, Juliette Albuisson, Marie-Agnès Collonge-Rame, Céline Populaire, Zohair Selmani, Amandine Baurand, Caroline Sawka, Geoffrey Bertolone, Patrick Callier, Yannis Duffourd, Philippe Jonveaux, Yves-Jean Bignon, Isabelle Coupier, François Cornelis, Christophe Cordier, Monique Mozelle-Nivoix, Jean-Baptiste Rivière, Paul Kuentz, Christel Thauvin, Romain Boidot, François Ghiringhelli, Marc O'Driscoll, Laurence Faivre, and Sophie Nambot from Université de Bourgogne, CHU Dijon Bourgogne, CHU Besançon, University of Sussex, Centre Georges François Leclerc, Université de Bourgogne-Franche Comté, Hôpitaux de Brabois, Centre Jean Perrin, ICM Val d’Aurel, Université Bordeaux, CHU de Bordeaux, CHRU de Strasbourg, and CHU-Reims used a combination of exome sequencing (ES), direct sequencing of Ataxia Telangiectasia and RAD3-related (ATR) in a replication cohort and prospective screening, followed by functional investigations, to report the identification of new candidate variants of ATR as predisposing to breast cancer (BC), including male breast cancer (MBC).“In the framework of the EX2TRICAN project, exploring unresolved extreme cancer phenotypes, we applied exome sequencing on rare familial cases with male breast cancer, identifying a novel pathogenic variant of ATR (p.Leu1808*).”ATR has already been suspected as being a predisposing gene to breast cancer in women. The researchers next identified 3 additional ATR variants in a cohort of both male and female with early onset and familial breast cancers (c.7762-2A>C; c.2078+1G>A; c.1A>G). Further molecular and cellular investigations showed impacts on transcripts for variants affecting splicing sites and reduction of ATR expression and phosphorylation of the ATR substrate CHEK1. This work further demonstrates the interest of an extended genetic analysis such as exome sequencing to identify very rare variants that can play a role in cancer predisposition in extreme phenotype cancer cases unexplained by classical cancer gene panels testing.“In conclusion, this work highlights the possible implication of ATR variants in male and female BC predisposition and shows the importance of extended genetic analysis in unsolved extreme phenotype cancer cases to identify rare alleles of biologically relevant candidate genes of cancer predisposition.”DOI: https://doi.org/10.18632/oncotarget.28358 Correspondence to: Sophie Nambot - sophie.nambot@chu-dijon.fr Keywords: male breast cancer, genetic predisposition to cancer, exome sequencing, ATR, extreme phenotype
Blog summary of an Editorial was published in Oncotarget, entitled, “Permeability and driving force: why is it difficult to control glycolytic flux by blocking lactate transporters?“_________________________________The process of glycolysis, or the conversion of glucose to energy in cells, is a critical component of many biological processes. This process is highly regulated, and glycolytic flux has been implicated in a variety of disease states, including cancer and diabetes. Despite significant advances in our understanding of glycolysis, researchers continue to find it difficult to control glycolytic flux.“Overall, glycolysis facilitates tumour proliferation and survival, and has become a hotly-pursued target for therapeutic inhibition.”In a new editorial paper, researchers Wiktoria Blaszczak and Pawel Swietach from the University of Oxford explored the challenges of this issue and potential solutions. On January 26, 2023, their editorial was published in Oncotarget and entitled, “Permeability and driving force: why is it difficult to control glycolytic flux by blocking lactate transporters?““In our recent study (Blaszczak et al. (2022)), using a panel of pancreatic ductal adenocarcinoma cell lines, we characterised how extracellular acidity feeds back to inhibit further glycolytic acid production [6].”Full blog - https://www.oncotarget.org/2023/02/16/controlling-glycolytic-flux-therapy-challenges-and-solutions/DOI - https://doi.org/10.18632/oncotarget.28351 (PDF Download)Correspondence to - Wiktoria Blaszczak - wiktoria.blaszczak@dpag.ox.ac.ukSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28351Keywords - MCT inhibitors, fermentative metabolism, lactate, PDAC, SLC16A1About OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/OncotargetYouTubeLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research paper was published in Oncotarget's Volume 14 on January 31, 2023, entitled, “Novel inflammation-combined prognostic index to predict survival outcomes in patients with gastric cancer.”In vivo inflammatory responses are involved in cancer growth, invasion and metastasis, and the involvement of systemic inflammatory responses and the surrounding microenvironment is intricately intertwined. In this recent study, researchers Noriyuki Hirahara, Takeshi Matsubara, Shunsuke Kaji, Hikota Hayashi, Yohei Sasaki, Koki Kawakami, Ryoji Hyakudomi, Tetsu Yamamoto, and Yoshitsugu Tajima from Shimane University Faculty of Medicine and Matsue Red Cross Hospital in Japan focused on the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), and devised an inflammation-combined prognostic index (ICPI) as a prognostic marker of cancer-specific survival (CSS).“We reviewed the clinicopathological data of 480 patients with gastric cancer undergoing curative laparoscopic gastrectomy between 2009 and 2019. This study examined the significance of LMR, NLR, PLR, and ICPI as cancer-specific prognostic markers.”In univariate analysis, tumor diameter, histological differentiation, pathological tumor-node-metastasis (pTNM) stage, LMR, NLR, PLR, C-reactive protein (CRP) level, carcinoembryonic antigen (CEA), and postoperative chemotherapy were significantly associated with CSS. In multivariate analysis, pTNM stage and CEA were the independent risk factors for CSS, although LMR, NLR, and PLR were not the independent risk factors for CSS.The ICPI formula was constructed using hazard ratios for three inflammation-based biomarkers with worse prognosis identified in the univariate analysis: LMR <4.315, NLR ≥2.344, and PLR ≥212.01, which were each scored as 1, with all remaining values pointed at 0. ICPI was calculated as follows: ICPI = 2.9 × LMR + 2.8 × NLR + 2.8 × PLR. The optimal cutoff value of ICPII was 2.9. On multivariate analysis, pTNM stage, CEA, and ICPI were independent prognostic factors for CSS. In the Kaplan–Meier survival analysis, CSS in the high ICPI group was significantly worse than that in the low ICPI group. ICPI was devised as a novel predictive index for prognosis, and its usefulness was clarified.“In this study, the ICPI was devised as a novel predictive index of prognosis, and its usefulness was clarified. However, it is still unclear how active preoperative intervention using the ICPI as an indicator will contribute to improved oncological prognosis. In the future, it will be necessary to conduct a multicenter prospective study to examine the prognostic effect of preoperative interventions, including nutrition.”DOI: https://doi.org/10.18632/oncotarget.28353 Correspondence to: Noriyuki Hirahara - norinorihirahara@yahoo.co.jp Keywords: gastric cancer, laparoscopic gastrectomy, novel predictive index, inflammation-combined prognostic index, cancer-specific survivalAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/OncotargetYouTubeLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research paper was published in Oncotarget's Volume 14 on February 2, 2023, entitled, “Everolimus downregulates STAT3/HIF-1α/VEGF pathway to inhibit angiogenesis and lymphangiogenesis in TP53 mutant head and neck squamous cell carcinoma (HNSCC).”TP53 mutant head and neck squamous cell carcinoma (HNSCC) patients exhibit poor clinical outcomes with 50–60% recurrence rates in advanced stage patients. In a recent phase II clinical trial, adjuvant therapy with everolimus (mTOR inhibitor) significantly increased 2-year progression-free survival in p53 mutated patients. TP53-driven mTOR activation in solid malignancies causes upregulation of HIF-1α and its target, downstream effector VEGF, by activating STAT3 cell signaling pathway. In this recent study, researchers Md Maksudul Alam, Janmaris Marin Fermin, Mark Knackstedt, Mackenzie J. Noonan, Taylor Powell, Landon Goodreau, Emily K. Daniel, Xiaohua Rong, Tara Moore-Medlin, Alok R. Khandelwal, and Cherie-Ann O. Nathan from LSU-Health Sciences Center investigated the effects of everolimus on the STAT3/HIF-1α/VEGF pathway in TP53 mutant cell lines and xenograft models. “The role of mTOR inhibitors (mTORi) as potent growth inhibitory and antiangiogenic/anti-lymphangiogenic agents in HNSCC is well established [18]. Moreover, mTORi significantly suppressed baseline invasiveness of endothelial and HNSCC tumor cells [19]. However, the underlying molecular mechanisms for mutant p53 protein-mediated activation of the mTOR pathway which drive the oncologic processes in HNSCC are yet to be elucidated.”Treatment with everolimus significantly inhibited cell growth in vitro and effectively reduced the growth of TP53 mutant xenografts in a minimal residual disease (MRD) model in nude mice. Everolimus treatment was associated with significant downregulation of STAT3/HIF-1α/VEGF pathway in both models. Further, treatment with everolimus was associated with attenuation in tumor angiogenesis and lymphangiogenesis as indicated by decreased microvessel density of vascular and lymphatic vessels in HN31 and FaDu xenografts. Everolimus downregulated the STAT3/HIF-1α/VEGF pathway to inhibit growth and in vitro tube formation of HMEC-1 (endothelial) and HMEC-1A (lymphatic endothelial) cell lines. “Our studies demonstrated that everolimus inhibits the growth of TP53 mutant tumors by inhibiting angiogenesis and lymphangiogenesis through the downregulation of STAT3/HIF-1α/VEGF signaling.”DOI: https://doi.org/10.18632/oncotarget.28355 Correspondence to: Cherie-Ann O. Nathan - cherieann.nathan@lsuhs.edu Keywords: TP53 mutant, HNSCC, angiogenesis, everolimus, mTORAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/OncotargetYouTubeLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research perspective was published in Oncotarget's Volume 14 on February 4, 2023, entitled, “The immunoregulatory protein CD200 as a potentially lucrative yet elusive target for cancer therapy.”CD200 is an immunoregulatory cell surface ligand with proven pro-tumorigenic credentials via its ability to suppress CD200 receptor (CD200R)-expressing anti-tumor immune function. This definitive role for the CD200-CD200R axis in regulating an immunosuppressive tumor microenvironment has garnered increasing interest in CD200 as a candidate target for immune checkpoint inhibition therapy. However, while the CD200 blocking antibody samalizumab is still in the early stages of clinical testing, alternative mechanisms for the pro-tumorigenic role of CD200 have recently emerged that extend beyond direct suppression of anti-tumor T cell responses and, as such, may not be susceptible to CD200 antibody blockade. In this new research perspective, researchers Anqi Shao and David M. Owens from Columbia University Irving Medical Center summarized the current understanding of CD200 expression and function in the tumor microenvironment as well as alternative strategies for potential neutralization of multiple CD200 mechanisms in human cancers.“In the future, unbiased genomic- and proteomic-based approaches may help to clarify these issues by identifying tumor-specific mechanisms of CD200 expression regulation across a variety of human cancers that may be leveraged for broader therapeutic benefit.”DOI: https://doi.org/10.18632/oncotarget.28354 Correspondence to: David M. Owens - do2112@cumc.columbia.edu Keywords: CD200 receptor, oncoimmunology, immunotherapy, tumor microenvironment, immune checkpoint inhibitionAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/OncotargetYouTubeLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Listen to a blog summary on a trending editorial published in Volume 14 of Oncotarget: “To be or not to be: the role of CD56 in multiple myeloma.”___________________________________________________________Multiple myeloma (MM) is a type of blood cancer that affects plasma cells in the bone marrow. These plasma cells, which are responsible for producing antibodies, become abnormal and begin to grow uncontrollably. This results in a buildup of abnormal cells in the bone marrow, leading to decreased production of healthy blood cells, bone damage and a host of other symptoms. MM is incredibly heterogenic, and this variability often leads to unsatisfactory long-term treatment outcomes in many patients with MM. Targets for new treatments and biomarkers of response are needed to improve patient outcomes. In a new editorial paper published in Oncotarget, researchers Francesca Cottini and Don Benson from The Ohio State University discuss a 2022 research paper they co-authored in which CD56 (or neuronal cell adhesion molecule; NCAM1) was thoroughly described as a biomarker and therapeutic target in multiple myeloma. On January 26, 2023, their editorial about this research paper was published in Oncotarget, entitled, “To be or not to be: the role of CD56 in multiple myeloma.”“Among others, CD56 is present at variable levels in approximately 70% of patients with multiple myeloma; however, very little is known about CD56 role in multiple myeloma.” (2022 Cottini et al.)Full blog - https://www.oncotarget.org/2023/02/02/the-importance-of-cd56-in-the-fight-against-multiple-myeloma/DOI - https://doi.org/10.18632/oncotarget.28350 (PDF Download)Correspondence to - Francesca Cottini - Francesca.cottini@osumc.eduSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28350Keywords - myeloma, targeted therapies, CD56, signalingAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/OncotargetYouTubeLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research paper was published in Oncotarget's Volume 14, entitled, “Spleen tyrosine kinase/FMS-like tyrosine kinase-3 inhibition in relapsed/refractory B-cell lymphoma, including diffuse large B-cell lymphoma: updated data with mivavotinib (TAK-659/CB-659).”Researchers Leo I. Gordon, Reem Karmali, Jason B. Kaplan, Rakesh Popat, Howard A. Burris III, Silvia Ferrari, Sumit Madan, Manish R. Patel, Giuseppe Gritti, Dima El-Sharkawi, F. Ian Chau, John Radford, Jaime Pérez de Oteyza, Pier Luigi Zinzani, Swaminathan P. Iyer, William Townsend, Harry Miao, Igor Proscurshim, Shining Wang, Shilpi Katyayan, Ying Yuan, Jiaxi Zhu, Kate Stumpo, Yaping Shou, Cecilia Carpio, and Francesc Bosch from Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, University College London Hospitals, Sarah Cannon Research Institute/Tennessee Oncology, Ospedale Papa Giovanni XXIII, University of Texas Health Science Center, Florida Cancer Specialists/Sarah Cannon Research Institute, Royal Marsden Hospital, The Christie NHS Foundation Trust and University of Manchester, Hospital Universitario HM Sanchinarro, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Università di Bologna, Houston Methodist Cancer Center, Takeda Development Center Americas, Inc. (TDCA), Vall d’Hebron Hospital Universitari, Universitat Autònoma de Barcelona, University of Texas MD Anderson Cancer Center, and Labcorp Drug Development report an updated analysis from a phase I study of the spleen tyrosine kinase (SYK) and FMS-like tyrosine kinase 3 inhibitor mivavotinib. They present data for the overall cohort of lymphoma patients and the subgroup of patients with diffuse large B-cell lymphoma (DLBCL), including an expanded cohort not included in the initial report.“Mivavotinib (TAK-659/CB-659) is an investigational, oral, reversible, potent dual inhibitor of spleen tyrosine kinase (SYK) and FMS-like tyrosine kinase 3 (FLT3) [18]. SYK is an essential component of the B-cell receptor signaling pathway; abnormal SYK signaling has been implicated in the pathogenesis of DLBCL and several other B-cell malignancies.”Patients with relapsed/refractory lymphoma for which no standard treatment was available received mivavotinib 60–120 mg once daily in 28-day cycles until disease progression/unacceptable toxicity. A total of 124 patients with lymphoma, including 89 with DLBCL, were enrolled. Overall response rates (ORR) in response-evaluable patients were 45% (43/95) and 38% (26/69), respectively. Median duration of response was 28.1 months overall and not reached in DLBCL responders. In subgroups with DLBCL of germinal center B-cell (GCB) and non-GCB origin, ORR was 28% (11/40) and 58% (7/12), respectively. Median progression free survival was 2.0 and 1.6 months in the lymphoma and DLBCL cohorts, respectively. Grade ≥3 treatment-emergent adverse events occurred in 96% of all lymphoma patients, many of which were limited to asymptomatic laboratory abnormalities; the most common were increased amylase (29%), neutropenia (27%), and hypophosphatemia (26%).“These findings support SYK as a potential therapeutic target for the treatment of patients with B-cell lymphomas, including DLBCL.”DOI: https://doi.org/10.18632/oncotarget.28352 Correspondence to: Leo I. Gordon - l-gordon@northwestern.edu About OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/OncotargetYouTubeLinkedIn - https://www.linkedin.com/company/oncotarget
A new research perspective was published in Oncotarget's Volume 14 on January 12, 2023, entitled, “Intraventricular immunovirotherapy; a translational step forward.”In this new perspective, researchers Joshua D. Bernstock, Sarah Blitz, Kyung-Don Kang, and Gregory K. Friedman from Harvard Medical School, Massachusetts Institute of Technology and University of Alabama at Birmingham discuss oncolytic virotherapy with intratumoral engineered type-1 herpes simplex virus (HSV). Intraventricular therapy (IVT) has been proven safe with promising efficacy in recent clinical trials for treatment of both pediatric and adult high-grade glioma. “Oncolytic herpes simplex virus type-1 (oHSV) has shown promise in clinical trials in both pediatric and adult brain tumors [6–9].”However, this approach excludes patients with tumors in surgically inaccessible and/or eloquent brain regions. Current delivery methods are also unable to access/treat those patients with metastatic disease in the spinal cord and/or leptomeningeal disease. A recent preclinical study has paved the way for clinical translation of intraventricular administration of oHSV by identifying and mitigating the toxicity associated with this route for therapeutic benefit in murine models of disseminated medulloblastoma. This work may ultimately allow for targeting of intractable disease and provides a feasible option for the repetitive dosing of clinically relevant immunovirotherapy, G207.“Overall, demonstrating the safety and efficacy of IVT with G207 is a significant step towards expanding the capabilities of oHSV, paving the way for new clinical trials, and increasing the potential of an already promising therapy.”DOI: https://doi.org/10.18632/oncotarget.28343 Correspondence to: Joshua D. Bernstock - jbernstock@bwh.harvard.edu, Gregory K. Friedman - gfriedman@uabmc.eduKeywords: oncolytic virotherapy, herpes simplex virus (HSV), G207, intraventricular therapy, leptomeningeal diseaseAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/OncotargetYouTubeLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research paper was published in Oncotarget's Volume 14 on January 12, 2023, entitled, “The chromatographic constitution of andiroba oil and its healing effects, compared to the LLLT outcomes, in oral mucositis induced in golden Syrian hamsters: a new treatment option.”The oral mucositis is a mucosal alteration that usually arises from oncological treatments, such as chemotherapy, and it is characterized as an inflammatory process. In this new study, researchers Jessica T. Gomes, Ana Márcia V. Wanzeler, Sergio M.A. Júnior, Rosa Helena F. Chaves Soares, Carolina P. de Oliveira, Emanuelle de M. Rodrigues, Bruno M. Soares, Diego D.F.A. Alcantara, Rommel M.R. Burbano, and Fabrício M. Tuji from Federal University of Pará and the University Center of Pará aimed to demonstrate the chromatographic constitution of Andiroba oil, while comparing and evaluating Andiroba oil and laser scarring efficiency in treatments of oral mucositis in hamsters. “The low-level laser therapy (LLLT) is the best standard treatment and the most efficient method in treating OM. Similarly, the andiroba oil presents great potential for the treatment of inflammatory diseases. Thus, this study aims to evaluate the healing and toxicological effects of andiroba oil, compared to the LLLT outcomes, observing if andiroba presents a similar/higher potential than the LLLT.”The animals were submitted to 5-Fluorouracil. Included in the study were total of 122 animals that were randomized and divided into the following groups: (a) positive control; (b) laser associated to andiroba oil; (c) laser; (d) andiroba oil; (e) negative control; (f) cyclophosphamide (genotoxicity control). The induction of oral mucositis occurred by the administration of intraperitoneal Fluorouracila (60 mg/kg) and trauma to the mucosa. The laser protocol was performed once a day and the andiroba oil applied 3 times a day (1,5 ml/day). The mucosae were photographed and removed for clinical and histopathological analysis on day 4, 8, 12, and 15. The analysis was based in OM severity, in specific scoring for the clinical and histopathological aspect. Toxicity was evaluated on day 15 using comet assay and it was performed by variant DNA damage parameters. The data were analyzed using analysis of variance (ANOVA) Tukey post-test and Kruskal–Wallis Dunn post-test. The “andiroba oil” and “laser” groups presented better results when compared to the control groups and the treatment associations. The andiroba oil presented the best scarring results, even considering its efficiency proximity to the laser treatment. “Andiroba and laser, separately, did not present genotoxicity, however their association evidences damage to DNA.”DOI: https://doi.org/10.18632/oncotarget.28338 Correspondence to: Diego D.F.A. Alcantara - diegoalcantara@globo.com Video: https://www.youtube.com/watch?v=wMwTGk7-VGUKeywords: phytotherapeutic drugs, medical oncology, stomatitis, wound healing, low-level light therapyAbout Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – https://www.youtube.com/@OncotargetJournal Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OASoundCloud – https://soundcloud.com/oncotargetFor media inquiries, please contact: media@impactjournals.com.
Listen to a blog summary of a trending research paper published in Volume 14 of Oncotarget: "Candidate drugs associated with sensitivity of cancer cell lines with DLST amplification or high mRNA levels."____________________________________________________Dihydrolipoamide S-succinyltransferase (DLST) is a crucial gene/protein/enzyme involved in the oxidative phosphorylation (OXPHOS) pathway and cellular energy production. Recent studies have demonstrated that, in neuroblastoma and triple-negative breast cancer (TNBC), increased expression of DLST is associated with increased tumor aggression and a poor disease prognosis. Researchers also found that, in leukemia and TNBC cell lines, the knockdown of DLST leads to apoptosis. These findings suggest that neuroblastoma and TNBC may benefit from DLST-inhibiting cancer therapy.In light of this evidence, researchers Christina Kuhn, Myriam Boeschen, Manuel Philip, Torsten Schöneberg, Doreen Thor, and Susanne Horn from the University of Leipzig, University Duisburg-Essen and the German Cancer Consortium investigated approved drugs that target DLST-activated tumors. In their recent study, the team used data from the Genomics of Drug Sensitivity in Cancer (GDSC) project to identify new drug candidates for the treatment of DLST-activated tumors. On January 12, 2023, their research paper was published in Oncotarget’s Volume 14, entitled, “Candidate drugs associated with sensitivity of cancer cell lines with DLST amplification or high mRNA levels.”“With the advent of complex genetic datasets of roughly 1000 cell lines in the Cancer Cell Line Encyclopedia (CCLE) and on drug resistance in the Genomics of Drug Sensitivity in Cancer project (GDSC), analyses of drug sensitivity have become possible on a larger scale [6, 7].”Full blog - https://www.oncotarget.org/2023/01/19/researchers-identify-new-drug-candidates-to-treat-dlst-tumors/DOI - https://doi.org/10.18632/oncotarget.28342Correspondence to - Christina Kuhn - Christina.Kuhn@medizin.uni-leipzig.deSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28342Keywords - neuroblastoma, drug sensitivity, drug resistance, drug repurposing, DLSTAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/OncotargetYouTubeLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/For media inquiries, please contact media@impactjournals.com.
A new research paper was published in Oncotarget's Volume 14 on January 12, 2023, entitled, “Targeting CD74 in B-cell non-Hodgkin lymphoma with the antibody-drug conjugate STRO-001.”Overexpression of CD74, a type II transmembrane glycoprotein involved in MHC class II antigen presentation, has been reported in many B-cell non-Hodgkin lymphomas (NHLs) and in multiple myeloma (MM). STRO-001 is a site-specific, predominantly single-species antibody-drug conjugate (ADC) that targets CD74 and has demonstrated efficacy in xenograft models of MM and tolerability in non-human primates. In this new study, researchers Xiaofan Li, Cristina Abrahams, Abigail Yu, Millicent Embry, Robert Henningsen, Venita DeAlmeida, Shannon Matheny, Toni Kline, Alice Yam, Ryan Stafford, Trevor Hallam, Mark Lupher, and Arturo Molina from Sutro Biopharma reported the results of preclinical studies designed to elucidate the potential role of STRO-001 in B-cell NHL. “In order to explore the potential of STRO-001 in NHL, in the present study we investigated CD74 expression in cell types found in bone marrow, evaluated its cytotoxicity in NHL cell lines, and assessed its antitumor efficacy and toxicity in xenograft models of NHL.”STRO-001 displayed nanomolar and sub-nanomolar cytotoxicity in 88% (15/17) of cancer cell lines tested. STRO-001 showed potent cytotoxicity on proliferating B cells while limited cytotoxicity was observed on naïve human B cells. A linear dose-response relationship was demonstrated in vivo for DLBCL models SU-DHL-6 and U2932. Tumor regression was induced at doses less than 5 mg/kg, while maximal activity with complete cures were observed starting at 10 mg/kg. In MCL Mino and Jeko-1 xenografts, STRO-001 starting at 3 mg/kg significantly prolonged survival or induced tumor regression, respectively, leading to tumor eradication in both models. “In summary, high CD74 expression levels in tumors, nanomolar cellular potency, and significant anti-tumor in DLBCL and MCL xenograft models support the ongoing clinical study of STRO-001 in patients with B-cell NHL.”DOI: https://doi.org/10.18632/oncotarget.28341 Correspondence to: Xiaofan Li - xli@sutrobio.com, Arturo Molina - amolina@sutrobio.com Keywords: CD74, antibody-drug conjugate, non-Hodgkin lymphoma, xenograft models, STRO-001About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – https://www.youtube.com/@OncotargetJournal Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OASoundCloud – https://soundcloud.com/oncotargetFor media inquiries, please contact: media@impactjournals.com.
A new research paper was published in Oncotarget’s Volume 13 on December 29, 2022, entitled, “Calcium signaling induced by 15-deoxy-prostamide-J2 promotes cell death by activating PERK, IP3R, and the mitochondrial permeability transition pore.”Melanoma is the deadliest form of skin cancer in the US. Although immunotherapeutic checkpoint inhibitors and small-molecule kinase inhibitors have dramatically increased the survival of patients with melanoma, new or optimized therapeutic approaches are still needed to improve outcomes. 15-deoxy-Δ12,14-prostamide J2 (15d-PMJ2) is an investigational small-molecule that induces ER stress-mediated apoptosis selectively in tumor cells. Additionally, 15d-PMJ2 reduces melanoma growth in vivo. To assess the chemotherapeutic potential of 15d-PMJ2, researchers Daniel A. Ladin, Margaret M. Nelson, Estefani Cota, Catherine Colonna, Colin Burns, Jacques Robidoux, Kelsey H. Fisher-Wellman, and Rukiyah Van Dross-Anderson from East Carolina University and University of North Carolina at Chapel Hill sought to uncover molecular pathways by which 15d-PMJ2 exerts its antitumor activity. B16F10 melanoma and JWF2 squamous cell carcinoma cell lines were cultured in the presence of pharmacological agents that prevent ER or oxidative stress as well as Ca2+ channel blockers to identify mechanisms of 15d-PMJ2 cell death. “Our data demonstrated the ER stress protein, PERK, was required for 15d-PMJ2-induced death.”PERK activation triggered the release of ER-resident Ca2+ through an IP3R sensitive pathway. Increased calcium mobilization led to mitochondrial Ca2+ overload followed by mitochondrial permeability transition pore (mPTP) opening and the deterioration of mitochondrial respiration. Finally, the researchers showed that the electrophilic double bond located within the cyclopentenone ring of 15d-PMJ2 was required for its activity. “The present study identifies PERK/IP3R/mPTP signaling as a mechanism of 15d-PMJ2 antitumor activity.”DOI: https://doi.org/10.18632/oncotarget.28334 Correspondence to: Rukiyah Van Dross-Anderson - vandrossr@ecu.edu Keywords: calcium, mitochondrial respiration, endoplasmic reticulum stress, cancer, prostamideAbout Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – https://www.youtube.com/@OncotargetJournal Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OASoundCloud – https://soundcloud.com/oncotargetFor media inquiries, please contact: media@impactjournals.com.
A new research paper was published in Oncotarget's Volume 13 on December 29, 2022, entitled, “Impact of Covid-19 on the management of patients with metastatic melanoma.”The Covid-19 pandemic created new uncertainties in the management of metastatic melanoma patients. In particular, the impact of immunotherapy, targeted therapy or chemotherapy on the risk of Sars-CoV-2 infection and severity was debated. In this study, researchers Michèle Welti, Phil F. Cheng, Joanna Mangana, Mitchell P. Levesque, Reinhard Dummer, and Laurence Imhof from University Hospital Zurich, University of Zurich and ETH Zurich analyzed all patients with metastatic melanoma receiving therapy at the Department of Dermatology at the University Hospital Zürich who developed Covid-19 between February 2020 and February 2022.“We retrospectively collected demographic data, cancer-specific parameters, melanoma treatment regimen, comorbidities and Covid-19-specific parameters in these patients.” Of the 350 patients with metastatic melanoma, 25 had Covid-19. The median age at the time of Covid-19 diagnosis was 66 years (range 36–86), 10 patients were female and 15 patients were male. The treatment regimen during infection was immunotherapy in 12 cases, followed by targeted therapy (n = 8), chemotherapy (n = 2) and TVEC injections, follow-up and palliative therapy in 1 case each. The severity was mild in 17 patients and 8 had a moderate to critical course. Patients with a severe Covid-19 course were often older and had more comorbidities than patients with a mild infection. Many of the patients had a mild Covid-19 course despite having metastatic melanoma and systemic therapy. “We therefore recommend continuing systemic therapy whenever possible, even in such exceptional situations as the Covid-19 pandemic.”DOI: https://doi.org/10.18632/oncotarget.28333 Correspondence to: Michèle Welti - michele.welti@uzh.ch Keywords: metastatic melanoma, Covid-19, Sars-CoV-2, immunotherapy, targeted therapyAbout Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – https://www.youtube.com/@OncotargetJournal Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OASoundCloud – https://soundcloud.com/oncotargetFor media inquiries, please contact: media@impactjournals.com.
A new research paper was published in Oncotarget's Volume 13 on December 20, 2022, entitled, “Resistance of MMTV-NeuT/ATTAC mice to anti-PD-1 immune checkpoint therapy is associated with macrophage infiltration and Wnt pathway expression.”One of the central challenges for cancer therapy is the identification of factors in the tumor microenvironment that increase tumor progression and immune tolerance. In breast cancer, fibrosis is a histopathologic criterion for invasive cancer and poor survival that results from inflammatory factors and remodeling of the extracellular matrix to produce an immune-tolerant microenvironment. In this new study, researchers Hongyan Yuan, Lu Jin, Handan Xiang, Anannya Bhattacharya, Philip E. Brandish, Gretchen Baltus, Alexander Tong, Changyan Zhou, and Robert I. Glazer from Georgetown University Medical Center, Merck Research Institute and Bicycle Therapeutics aimed to determine whether tolerance is associated with the immune checkpoint, Programmed Cell Death 1 (PD-1). A conditional model of mammary fibrosis recently developed by this team, NeuT/ATTAC mice, were administered a murine-specific anti-PD-1 mAb related to pembrolizumab. The researchers monitored drug response by tumor development, imaging mass cytometry, immunohistochemistry, and tumor gene expression by RNAseq. “Utilizing this more stringent tumor model to test its susceptibility to anti-PD-1 immunotherapy, we report the signaling processes associated with its lack of responsiveness.”Tumor progression in NeuT/ATTAC mice was unaffected by weekly injection of anti-PD-1 over four months. Insensitivity to anti-PD-1 was associated with several processes, including increased tumor-associated macrophages (TAM), epithelial to mesenchymal transition (EMT), fibroblast proliferation, an enhanced extracellular matrix and the Wnt signaling pathway, including increased expression of Fzd5, Wnt5a, Vimentin, Mmp3, Col2a1, and Tgfβ1. These results suggest potential therapeutic avenues that may enhance PD-1 immune checkpoint sensitivity, including the use of tumor microenvironment targeted agents and Wnt pathway inhibitors.“Overall, the immune tolerant TME in NeuT/ATTAC mice was associated with tumor-infiltrating macrophages, Foxp3+/PD-1- Treg cells as well as upregulation of the Wnt signaling pathway, which may provide further insights into the therapeutic options that may enhance immune checkpoint therapy.”DOI: https://doi.org/10.18632/oncotarget.28330 Correspondence to: Robert I. Glazer - glazerr@georgetown.edu Keywords: PD-1, NeuT, Wnt, macrophages, mammary tumorigenesisAbout Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTubeInstagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OASoundCloud - https://soundcloud.com/oncotargetFor media inquiries, please contact: media@impactjournals.com.
Listen to a blog summary of a trending research paper published by Oncotarget: "Anti-tumor effect of antibody drug conjugate ASP1235 targeting Fms-like tyrosine kinase 3 with venetoclax plus azacitidine in an acute myeloid leukemia xenograft mouse model."_________________________________________________________The average age of patients with acute myeloid leukemia (AML) is 67 years old. Older adults generally have a lower tolerance for treatments that exhibit high off-target toxicity. Additionally, chemotherapy-relapsed or -refractory (R/R) AML patients are often at an advanced stage of disease and are therefore more likely to have comorbidities that may reduce their tolerance for harsh treatments.Thus, pharmaceutical AML drugs with high efficacy and low toxicity are in high demand. Antibody drug conjugates (ADCs) are emerging as promising therapeutic approaches to more safely treat hematological malignancies by reducing side effects. ADCs are designed to decrease damage to healthy tissues by specifically targeting tumor-associated antigens attached to cancer cells.“Antibody drug conjugates (ADC) are one of the modalities that aims to dissociate drug efficacy from toxicity. ADC consists of three components: antibody specific for tumor associated antigen, drug linker and cytotoxic payload.”ASTELLAS PHARMARecently, researchers from Astellas Pharma Inc. (a pharmaceutical company in Japan) developed ASP1235—a novel ADC that targets Fms-like tyrosine kinase 3 (FLT3). In more than 90% of AML patients, FLT3 is overexpressed on leukemic blasts. ASP1235 is designed to target FLT3-positive leukemia cells and deliver the cytotoxic drug payload to these cells. However, this drug alone was found to have only a mild effect on AML cells, prompting researchers to assess the efficacy of ASP1235 in combination with other drugs.In a new study, Astellas Pharma researchers Hirofumi Tsuzuki, Tatsuya Kawase, Taisuke Nakazawa, Masamichi Mori, and Taku Yoshida investigated the efficacy of ASP1235 combined with venetoclax (an anti-apoptotic agent) and azacitidine (a DNA methyltransferase inhibitor) in an experimental mouse model of AML. Their research paper was published in Oncotarget on December 20, 2022, and entitled, “Anti-tumor effect of antibody drug conjugate ASP1235 targeting Fms-like tyrosine kinase 3 with venetoclax plus azacitidine in an acute myeloid leukemia xenograft mouse model.”Full blog: https://www.oncotarget.org/2023/01/04/novel-antibody-drug-conjugate-improves-murine-acute-myeloid-leukemia/DOI: https://doi.org/10.18632/oncotarget.28331Corresponding author: Hirofumi Tsuzuki - hirofumi.tsuzuki@astellas.comKeywords: acute myeloid leukemia (AML), ASP1235, antibody drug conjugate (ADC), venetoclax, azacitidineAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/OncotargetYouTubeLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research paper was published in Oncotarget's Volume 13 on December 17, 2022, entitled, “Serum microRNAs as new criteria for referral to early palliative care services in treatment-naïve advanced cancer patients.”A major obstacle to the implementation of early palliative care (EPC) is the lack of objective criteria for referral to EPC. Circulating microRNAs (miRNAs) have been recognized as promising biomarkers. In the current study, researchers Tomofumi Miura, Shuichi Mitsunaga, Juntaro Matsuzaki, Satoko Takizawa, Ken Kato, Atsushi Ochiai, and Takahiro Ochiya from National Cancer Center Research Institute, National Cancer Center Hospital, Keio University, Toray Industries, Inc., and Tokyo Medical University investigated objective definitions for referral to EPC using microRNA. A total of 178 serum samples were obtained from patients with lung, gastrointestinal, colorectal, bile duct, pancreas, and bladder cancers who were treatment-naïve and received chemotherapy between January 2011 and December 2013 at National Cancer Center Hospital East. “The aim of the present study was to develop predictive models using serum miRNAs for patients who [were] admitted to a PCU [palliative care unit] ≤6 months after starting anti-tumor treatment.”The team investigated expression levels of miRNAs using microarrays. The primary outcome was prediction of admission to a palliative care unit ≤6 months after first visit. Diagnostic models using clinical characteristics, miRNAs and combinations of both were constructed. The miRNA models were constructed using 6 miRNA levels. The best areas under the receiver operating characteristic curve (AUCs) of the clinical model was 0.741, while the average AUCs of miRNA-based models and combination models were 0.769 and 0.806, respectively. Combination models showed higher AUCs than the clinical model (p < 0.023). The researchers assert that the present combination models might offer new objective definitions for referral to EPC and thus contribute to real-world implementation of EPC.“The present study developed a predictive model using miRNA for patients admitted to a PCU ≤6 months after starting anti-tumor treatment. The present models might offer objective criteria for oncologists to facilitate the referral of patients to the EPC.”DOI: https://doi.org/10.18632/oncotarget.28327 Correspondence to: Shuichi Mitsunaga - smitsuna@east.ncc.go.jp Keywords: microRNA, early palliative care, integration, cancer, referralAbout Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTubeInstagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OASoundCloud - https://soundcloud.com/oncotargetFor media inquiries, please contact: media@impactjournals.com.
A new research paper was published in Oncotarget's Volume 13 on December 17, 2022, entitled, “The role of pyrethroid derivatives in autophagy and apoptosis crosstalk signaling and potential risk for malignancies.”Pyrethroids are extensively used insecticides by virtue of insecticidal activity potential in Asia, especially India, and in different nations worldwide to counter mosquitoes and insects for household or agricultural needs. The continuous widespread and uncontrolled use of pyrethroids and its derivatives have influenced multiple deleterious effects resulting in a potential risk factor causing damage to organ systems. Allethrin and prallethrin are extensively used, yet their influences on human primary cells are very limited or under-reported. The potential mechanisms by which allethrin and prallethrin modulates human primary cells, especially the molecular mechanisms or interconnectivity of autophagy-apoptosis, their clinical relevance in human subjects or patients are not well defined. In the current study, researchers Jyothi Puvula, Narendra Maddu, Nagajothi Gutam, Asha Parimal, and Raghavendra B. Pongali from Sri Krishnadevaraya University, Queen Mary’s College, Manipal University, and National Institute of Biomedical Genomics furnished the evidence that both allethrin and prallethrin user samples significantly induced Ccl2 mRNA expression, increased amount of reactive oxygen intermediate, inhibited membrane bound enzymes and altered membrane fluidity. Pyrethroid derivative users had induced levels of lipid peroxidation and induced binding activities of transcription factors(tfs) like CEBP-β and NF-AT. Pyrethroid derivatives induced autophagy, elicited intracellular Ca2+ concentration, calcineurin and regulated proapoptotic genes, DAPK1, Bim. “Our current study presumably comprises the initial investigation of a very new mechanism of pyrethroid derivatives-moderated programmed cell death in various cell sets or types, like human primary cells where-in this is a late event, is documented.” Hence, the current research study might be significant in the various pyrethroid derivatives-allied hematological-related cancers and immunosuppressant or auto-immune disorders. In the foremost instance, the researchers present data stating that pyrethroid derivatives induces multiple cell signaling cascades, like CEBP-β, NF-AT, ERK and MAPK having a role in autophagy thereby; synchronously effectively impact on the apoptosis, therefore causing hematological tumors and toxic or immune related disorders. “Overall this current study might facilitate to formulate therapeutics or intervention targets that might serve to decrease the effect or impact of pyrethroids derivatives by targeting the signaling cascade that serves to minimize the modulation of autophagy mediated apoptosis.”DOI: https://doi.org/10.18632/oncotarget.28328 Correspondence to: Raghavendra B. Pongali - raghavbiot@gmail.com Keywords: allethrin, prallethrin, autophagy, apoptosis, Ccl2About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTubeInstagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OASoundCloud - https://soundcloud.com/oncotargetFor media inquiries, please contact: media@impactjournals.com.
A new research paper was published in Oncotarget's Volume 13 on December 6, 2022, entitled, “Plasma growth hormone is a potential biomarker of response to atezolizumab and bevacizumab in advanced hepatocellular carcinoma patients.”Hepatocellular carcinoma (HCC) has limited systemic therapy options when discovered at an advanced stage. Thus, there is a need for accessible and minimally invasive biomarkers of response to guide the selection of patients for treatment.In this new study, researchers Yehia I. Mohamed, Dan G. Duda, Muhammad O. Awiwi, Sunyoung S. Lee, Lina Altameemi, Lianchun Xiao, Jeffrey S. Morris, Robert A. Wolff, Khaled M. Elsayes, Rikita I. Hatia, Aliya Qayyum, Shadi M. Chamseddine, Asif Rashid, James C. Yao, Armeen Mahvash, Manal M. Hassan, Hesham M. Amin, and Ahmed Omar Kaseb from MD Anderson Cancer Center, Massachusetts General Hospital, Harvard Medical School, Michigan State University, University of Pennsylvania, and Perelman School of Medicine investigated the biomarker value of plasma growth hormone (GH) level as a potential biomarker to predict outcome in unresectable HCC patients treated with current standard therapy, atezolizumab plus bevacizumab (Atezo/Bev).“The present study was designed to investigate the association between GH levels and overall survivals (OS) and progression free survival (PFS) in HCC patients treated with current standard, atezolizumab plus bevacizumab.”The study included unresectable HCC patients scheduled to receive Atezo/Bev. Patients were followed to determine progression-free survival (PFS) and overall survival (OS). Plasma GH levels were measured by ELISA and used to stratify the HCC patients into GH-high and GH-low groups (the cutoff normal GH levels in women and men are ≤3.7 μg/L and ≤0.9 μg/L, respectively). The Kaplan-Meier method was used to calculate median OS and PFS and Log rank test was used to compare survival outcomes between GH-high and -low groups.Thirty-seven patients were included in this analysis, of whom 31 were males and 6 females, with a median age of 67 years (range: 37–80). At the time of the analysis, the one-year survival rate was 70% (95% CI: 0.51, 0.96) among GH low patients and 33% (95% CI: 0.16, 0.67) among GH high patients. OS was significantly superior in GH-low compared to GH-high patients (median OS: 18.9 vs. 9.3 months; p = 0.014). PFS showed a non-significant trend in favor of GH-low patients compared to the GH-high group (median PFS: 6.6 vs. 2.9 months; p = 0.053).“Plasma GH is a biomarker candidate for predicting treatment outcomes in advanced HCC patients treated with Atezo/Bev. This finding should be further validated in larger randomized clinical trials in advanced HCC patients.”DOI: https://doi.org/10.18632/oncotarget.28322 Correspondence to: Ahmed Omar Kaseb - akaseb@mdanderson.orgKeywords: growth hormone, hepatocellular carcinoma, immunotherapy, atezolizumab, bevacizumabAbout Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OASoundCloud – https://soundcloud.com/oncotargetFor media inquiries, please contact: media@impactjournals.com.
Listen to a blog summary of an editorial perspective published in Volume 13, entitled, "The future of bioorthogonal-chemistry for targeting of exosomes in precision medicine."____________________________________________________________Extracellular vesicles are membrane-bound vehicles released by cells into the extracellular environment. There are three known types of extracellular vesicles: microvesicles, apoptotic bodies and exosomes. Discovered in 1983, exosomes can be defined as packets of bio-nanoparticles released by cells containing bioactive molecules such as proteins, lipids and nucleic acids. Exosomes can deliver their payload to other cells and are now also recognized for their role in cell-to-cell communication. This makes exosomes attractive targets for precision medicine tactics. However, targeting exosomes is challenging due to their nano-size and reactive contents. Bioorthogonal-chemistry may provide a new approach for targeting exosomes in precision medicine.“Bioorthogonal is the name of a chemical reaction that can occur inside of living cells without interfering the naïve biological process [1, 2].”Bioorthogonal-chemistry allows for the attachment of bioactive molecules to the surface of exosomes without disturbing the native environment. Developed in the early 2000s, this strategy could potentially be used to deliver therapeutic drugs or bioactive molecules directly to the target site with high precision. Bioorthogonal-chemistry is still at an early stage of development, but it holds promise in precision medicine for the treatment of cancer and other illnesses. By providing a way to target exosomes with bioactive molecules, bioorthogonal-chemistry could help to significantly improve the efficacy of medical treatments. It could also reduce the side effects of current treatments and increase safety for patients.“The concept of bioorthogonal chemistry has inspired a generation of biologists to think about RNA editing and bioengineering of exosomes [3, 4].”Full blog - https://www.oncotarget.org/2022/12/20/a-new-method-of-targeting-exosomes-in-precision-medicine/DOI - https://doi.org/10.18632/oncotarget.28323Correspondence to - Mujib Ullah - ullah@stanford.edu About OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/OncotargetYouTubeLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/For media inquiries, please contact: media@impactjournals.com
Dr. Kerri Winters-Stone and Dr. Jacob Raber from Oregon Health and Science University, Portland, OR, describe a recent research paper they co-authored that was published by Oncotarget in Volume 13, entitled, “Association of fall rate and functional status by APOE genotype in cancer survivors after exercise intervention.”DOI - https://doi.org/10.18632/oncotarget.28310Correspondence to - Jacob Raber - raberj@ohsu.eduVideo - https://www.youtube.com/watch?v=XQK7MK7qfWYAbstractPurpose/Objectives: Cancer treatment survivors often report impaired functioning and increased falls. Not all survivors experience the same symptom burden, suggesting individual susceptibilities. APOE genotype is a potential genetic risk factor for cancer treatment related side effects. Lifestyle factors such as physical activity can mitigate the effect of APOE genotype on measures of clinical interest in individuals without a history of cancer. We tested the hypothesis that APOE genotype influences cancer treatment related side effects and symptoms as well as response to exercise intervention.Materials and Methods: Data from a subsample of a study of fall prevention exercise in post-treatment female cancer survivors aged 50–75 years old (https://clinicaltrials.gov NCT01635413) were used to conduct a secondary data analysis. ApoE genotype was determined by serum sampling. Physical functioning, frequency of falls, and symptom burden were assessed using survey instruments.Results: Data from 126 female cancer survivors a median of 49 months out from cancer diagnosis were analyzed. ApoE4 carriers trended toward a higher fall rate at baseline (p = 0.059), but after exercise intervention had a fall rate lower than E4 non-carriers both immediately after structured intervention (p = 0.013) and after 6 months of follow up (p = 0.002). E2 carriers did not show improved measures of depressive symptoms and self-report disability after exercise intervention. E3 homozygotes showed increased self report physical activity after the 6 month exercise intervention, but E4 and E2 carriers did not.Conclusions: APOE genotype may modulate cancer treatment related side effects and symptoms and response to exercise intervention.Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28310Press release - https://www.oncotarget.com/news/pr/oncotarget-association-of-fall-rate-and-functional-status-by-apoe-genotype-in-cancer-survivors-after-exercise-intervention/Keywords - apoE, breast cancer, exercise intervention, fall rate, functional statusAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/OncotargetYouTubeLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
Listen to a blog summary of a trending research paper published in Volume 13, entitled, “Plasma growth hormone is a potential biomarker of response to atezolizumab and bevacizumab in advanced hepatocellular carcinoma patients.”__________________________________________________Hepatocellular carcinoma (HCC) is a highly aggressive cancer of the liver with a very poor prognosis; many patients pass away within a year of diagnosis. Currently, there is no effective screening method for HCC and thus, 80% of patients are diagnosed at advanced stages. This makes treatment difficult and often unsuccessful. As a result, new treatments for HCC are constantly being explored.Atezolizumab and bevacizumab are two standard therapies used to treat unresectable, advanced HCC. However, researchers Yehia I. Mohamed, Dan G. Duda, Muhammad O. Awiwi, Sunyoung S. Lee, Lina Altameemi, Lianchun Xiao, Jeffrey S. Morris, Robert A. Wolff, Khaled M. Elsayes, Rikita I. Hatia, Aliya Qayyum, Shadi M. Chamseddine, Asif Rashid, James C. Yao, Armeen Mahvash, Manal M. Hassan, Hesham M. Amin, and Ahmed Omar Kaseb from MD Anderson Cancer Center, Massachusetts General Hospital, Harvard Medical School, Michigan State University, and University of Pennsylvania Perelman School of Medicine noticed a significant gap in research on biomarkers of response in advanced HCC patients treated with atezolizumab plus bevacizumab. The team conducted a new study aimed at beginning to close this gap. On December 6, 2022, their research paper was published in Oncotarget’s Volume 13, entitled, “Plasma growth hormone is a potential biomarker of response to atezolizumab and bevacizumab in advanced hepatocellular carcinoma patients.”“This study investigated the biomarker value of plasma growth hormone (GH) level as a potential biomarker to predict outcome in unresectable HCC patients treated with current standard therapy, atezolizumab plus bevacizumab (Atezo/Bev).”Full blog - https://www.oncotarget.org/2022/12/08/plasma-growth-hormone-in-hcc-a-biomarker-of-response-to-atezo-bev/DOI - https://doi.org/10.18632/oncotarget.28322Correspondence to - Ahmed Omar Kaseb - akaseb@mdanderson.org Video - https://www.youtube.com/watch?v=r2_6kjhwOfMSign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28322Keywords - growth hormone, hepatocellular carcinoma, immunotherapy, atezolizumab, bevacizumabAbout OncotargetOncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:SoundCloud - https://soundcloud.com/oncotargetFacebook - https://www.facebook.com/Oncotarget/Twitter - https://twitter.com/oncotargetInstagram - https://www.instagram.com/oncotargetjrnl/YouTube - https://www.youtube.com/OncotargetYouTubeLinkedIn - https://www.linkedin.com/company/oncotargetPinterest - https://www.pinterest.com/oncotarget/Reddit - https://www.reddit.com/user/Oncotarget/Media ContactMEDIA@IMPACTJOURNALS.COM18009220957
A new research paper was published in Oncotarget's Volume 13 on December 6, 2022, entitled, “Expression of p-STAT3 and c-Myc correlates with P2-HNF4α expression in nonalcoholic fatty liver disease (NAFLD).”Nonalcoholic fatty liver disease (NAFLD) is associated with the metabolic syndrome and is rapidly becoming one of the major causes of hepatic cirrhosis and hepatocellular carcinoma (HCC), although some cases of HCC have developed in non-cirrhotic livers [1–8]. Although the percentage of patients with NAFLD who ultimately progress to fibrosis and later to HCC is relatively small, the number is significant because of the sheer number of patients who have NAFLD. Because there are no reliable biomarkers to predict the risk of HCC in patients with NAFLD, designing effective and cost-effective surveillance programs aimed at prevention and early detection of HCC is difficult, if not impossible. Therefore, there is an urgent need to identify such biomarkers and especially those that may appear at different stages of progression toward HCC.In the current study, researchers Mamoun Younes, Lin Zhang, Baharan Fekry, and Kristin Eckel-Mahan from George Washington University School of Medicine and Health Sciences and McGovern Medical School at the University of Texas Health Science Center (UTHealth) studied the expression of two hepatocyte nuclear factor 4 alpha (HNF4α) isoforms, p-STAT3. and c-Myc in 49 consecutive liver biopsies with nonalcoholic fatty liver disease (NAFLD) using immunohistochemistry. “The aim of this study was to determine the relationships between p-STAT3, c-Myc and P2-HNF4α expression in biopsies from livers with NAFLD as potential biomarkers of HCC risk.”All 49 biopsies (100%) were positive for nuclear expression of P1-HNF4α. Twenty-eight (57%) cases were positive for P2-HNF4α, 6 (12%) were positive for p-STAT3 and 5 (10%) were positive for c-Myc. All 6 (100%) p-STAT3-positive cases were also positive for P2-HNF4α (p = 0.03). p-STAT3-positive cases were more likely to be positive for c-Myc (67% vs. 2%, p = 0.0003). Four cases were positive for P2-HNF4α, p-STAT3 and c-Myc. p-STAT3 expression was associated with hypertension (p = 0.037). All c-Myc positive biopsies were from patients with obesity, diabetes and hypertension. Only c-Myc expression was associated with advanced fibrosis; three (60%) of the c-Myc positive cases were associated with advanced fibrosis in contrast to 7 (10%) of the 44 c-Myc negative cases (p = 0.011). “Based on these results, we hypothesize with the following sequence of events with progression of NAFLD: P2-HNF4α expression is followed by expression of p-STAT3 which in turn is followed by the expression of c-Myc. Additional larger studies are needed to confirm these findings.”DOI: https://doi.org/10.18632/oncotarget.28324 Correspondence to: Mamoun Younes - myounes@mfa.gwu.edu Keywords: hepatocyte nuclear factor four alpha, steatohepatitis, immunohistochemistry, hepatocellular carcinoma, isoformTo learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTubeInstagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OASoundCloud - https://soundcloud.com/oncotargetFor media inquiries, please contact: media@impactjournals.com
A new research paper was published in Oncotarget's Volume 13 on November 22, 2022, entitled, “Essential amino acids as diagnostic biomarkers of hepatocellular carcinoma based on metabolic analysis.”Metabolomics, defined as the comprehensive identification of all small metabolites in a biological sample, has the power to shed light on phenotypic changes associated with various diseases, including cancer. In the current study, researchers Yuji Morine, Tohru Utsunomiya, Hisami Yamanaka-Okumura, Yu Saito, Shinichiro Yamada, Tetsuya Ikemoto, Satoru Imura, Shohei Kinoshita, Akiyoshi Hirayama, Yasuhito Tanaka, and Mitsuo Shimada from Tokushima University Graduate School, Keio University and Kumamoto University used metabolomics to discover potential biomarkers of hepatocellular carcinoma (HCC). The team investigated the metabolomes of tumor and non-tumor tissue in 20 patients with primary HCC using capillary electrophoresis–time-of-flight mass spectrometry. They also analyzed blood samples taken immediately before and 14 days after hepatectomy to identify associated changes in the serum metabolome. “In the present study, we sought to discover reliable metabolomic biomarkers for HCC diagnosis by elucidating metabolic alterations in primary HCC tumor tissue compared with non-tumor tissue, and additionally by investigating the serum metabolomic profiles before and after curative hepatectomy.”Marked changes were detected in the different quantity of 61 metabolites that could discriminate between HCC tumor and paired non-tumor tissue and additionally between HCC primary tumors and colorectal liver metastases. Among the 30 metabolites significantly upregulated in HCC tumors compared with non-tumor tissues, 10 were amino acids, and 7 were essential amino acids (EAA) (leucine, valine, tryptophan, isoleucine, methionine, lysine, and phenylalanine). Similarly, the serum metabolomes of HCC patients before hepatectomy revealed a significant increase in 16 metabolites, including leucine, valine, and tryptophan. The results of this study revealed striking differences in the metabolomes of HCC tumor tissue compared with non-tumor tissue, and identified the essential amino acids leucine, valine, and tryptophan as potential metabolic biomarkers for HCC.“In this study, the major findings were (i) the metabolomic profile of HCC tumors differs not only compared with matched non-tumor liver tissue but also with CRLM tissue, (ii) the serum metabolome of HCC patients is altered by hepatectomy, and (iii) the three EAAs leucine, valine, and tryptophan are candidate metabolomic biomarkers for hepatocarcinogenesis. Notably, however, we found that the metabolic profiles of HCC tumor tissues of differing etiologies (HBV/HCV infection) could not be distinguished, nor could the profiles of non-tumor liver tissue from any of the patient subgroups.”DOI: https://doi.org/10.18632/oncotarget.28306 Correspondence to: Yuji Morine - ymorine@tokushima-u.ac.jp Keywords: metabolomics, essential amino acid, hepatocellular carcinoma, diagnostic biomarkerTo learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTubeInstagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OASoundCloud - https://soundcloud.com/oncotargetFor media inquiries, please contact: media@impactjournals.com
A new review was published in Oncotarget’s Volume 13 on November 17, 2022, entitled, “Myeloid-derived suppressor cells: Cancer, autoimmune diseases, and more.”
Although cancer immunotherapy using immune checkpoint inhibitors (ICIs) has been recognized as one of the major treatment modalities for malignant diseases, the clinical outcome is not uniform in all cancer patients. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells that possess various strong immunosuppressive activities involving multiple immunocompetent cells that are significantly accumulated in patients who did not respond well to cancer immunotherapies.
In this new review paper, researchers Masahiko Shibata, Kotaro Nanno, Daigo Yoshimori, Takahiro Nakajima, Makoto Takada, Takashi Yazawa, Kousaku Mimura, Norio Inoue, Takafumi Watanabe, Kazunoshin Tachibana, Satoshi Muto, Tomoyuki Momma, Yoshiyuki Suzuki, Koji Kono, Shungo Endo, and Seiichi Takenoshita from Fukushima Medical University, Aizu Chuo Hospital, Aizu Oncology Consortium, Nippon Medical School, and Bange Kousei General Hospital reviewed the perspective of MDSCs with emerging evidence.
“Here, we review the following: the phenotypes and origins of MDSCs; the mechanisms of immunosuppression by MDSCs; MDSC functions in the TME; MDSCs in benign disorders and physiology; and consideration of MDSC manipulation in cancer treatment.”
Many studies on MDSCs were performed in malignant diseases. Substantial studies on the participation of MDSCs on non-malignant diseases such as chronic infection and autoimmune diseases, and physiological roles in obesity, aging, pregnancy and neonates have yet to be reported. With the growing understanding of the roles of MDSCs, variable therapeutic strategies and agents targeting MDSCs are being investigated, some of which have been used in clinical trials. More studies are required in order to develop more effective strategies against MDSCs.
ICI therapies have been developed and demonstrated surprising outcomes in many types of cancer. However, the effects of ICIs are not universal or uniformal in all cancer patients, and emerging evidence has indicated that MDSCs are a crucial target to overcome this important issue with a growing understanding of the roles of MDSCs, variable therapeutic strategies and agents targeting MDSCs are under exploration, some of which have been used in clinical trials.
“More studies are required for the development of more effective strategies against MDSCs.”
DOI: https://doi.org/10.18632/oncotarget.28303
Correspondence to: Masahiko Shibata - mshibata@fmu.ac.jp
Video: https://youtu.be/ZJj6CzcJ6x4
Keywords: MDSC, immunosuppression, Treg, TAM, cancer
About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com.
A new research perspective was published in Oncotarget's Volume 13 on November 17, 2022, entitled, “Treasures from trash in cancer research.”
Cancer research has significantly improved in recent years, primarily due to next-generation sequencing (NGS) technology. Consequently, an enormous amount of genomic and transcriptomic data has been generated. In most cases, the data needed for research goals are used, and unwanted reads are discarded. However, these eliminated data contain relevant information. Aiming to test this hypothesis, genomic and transcriptomic data were acquired from public datasets.
In this new research perspective, researchers Fabiano Cordeiro Moreira, Dionison Pereira Sarquis, Jorge Estefano Santana de Souza, Daniel de Souza Avelar, Taíssa Maria Thomaz Araújo, André Salim Khayat, Sidney Emanuel Batista dos Santos, and Paulo Pimentel de Assumpção from Instituto Metrópole Digital at the Universidade Federal do Rio Grande do Norte and Núcleo de Pesquisas em Oncologia and Instituto de Ciências Biológicas at the Universidade Federal do Pará used metagenomic tools to explore genomic cancer data; additional annotations were used to explore differentially expressed ncRNAs from miRNA experiments, and variants in adjacent to tumor samples from RNA-seq experiments were also investigated.
“Here, we demonstrate potential strategies to benefit from nontargeted information resulting from high-throughput cancer investigations.”
In all analyses, new data were obtained: from DNA-seq data, microbiome taxonomies were characterized with a similar performance of dedicated metagenomic research; from miRNA-seq data, additional differentially expressed sncRNAs were found; and in tumor and adjacent to tumor tissue data, somatic variants were found.
These findings indicate that unexplored data from NGS experiments could help elucidate carcinogenesis and discover putative biomarkers with clinical applications. Further investigations should be considered for experimental design, providing opportunities to optimize data, saving time and resources while granting access to multiple genomic perspectives from the same sample and experimental run.
“Altogether, our results strengthen the hypothesis that abundant additional and potentially useful information can be extracted from NGS. Moreover, the integrated investigation of every available information should provide a broader and more robust interpretation of the molecular scenario from each experiment.”
DOI: https://doi.org/10.18632/oncotarget.28308
Correspondence to: Paulo Pimentel de Assumpção - assumpcaopp@gmail.com
Video: https://www.youtube.com/watch?v=etqlRWCdhI0
Keywords: cancer metagenomics, cancer sncRNA expression, RNA-Seq variant calling
About Oncotarget:
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com
A new research paper was published in Oncotarget’s Volume 13 on November 17, 2022, entitled, “Association of fall rate and functional status by APOE genotype in cancer survivors after exercise intervention.”
Cancer treatment survivors often report impaired functioning and increased falls. Not all survivors experience the same symptom burden, suggesting individual susceptibilities. APOE genotype is a potential genetic risk factor for cancer treatment related side effects. Lifestyle factors such as physical activity can mitigate the effect of APOE genotype on measures of clinical interest in individuals without a history of cancer.
In this new study, researchers Gwendolyn J. McGinnis, Sarah Holden, Betty Yu, Charlton Ransom, Carolyn Guidarelli, Brian De, K Diao, David Boyce, Charles R. Thomas Jr., Kerri Winters-Stone, and Jacob Raber from the University of Texas MD Anderson Cancer Center, Oregon Health and Science University and Dartmouth-Hitchcock’s Dartmouth Cancer Center tested the hypothesis that APOE genotype influences cancer treatment related side effects and symptoms as well as response to exercise intervention.
“In the current analyses, the modulating effect of apoE genotype on functional status and symptom burden in response to exercise intervention was investigated in a subsample of trial participants.”
Data from a subsample of a study of fall prevention exercise in post-treatment female cancer survivors aged 50–75 years old (https://clinicaltrials.gov NCT01635413) were used to conduct a secondary data analysis. ApoE genotype was determined by serum sampling. Physical functioning, frequency of falls, and symptom burden were assessed using survey instruments.
Data from 126 female cancer survivors a median of 49 months out from cancer diagnosis were analyzed. ApoE4 carriers trended toward a higher fall rate at baseline (p = 0.059), but after exercise intervention had a fall rate lower than E4 non-carriers both immediately after structured intervention (p = 0.013) and after 6 months of follow up (p = 0.002). E2 carriers did not show improved measures of depressive symptoms and self-report disability after exercise intervention. E3 homozygotes showed increased self report physical activity after the 6 month exercise intervention, but E4 and E2 carriers did not.
“The study findings suggest that APOE genotype may be associated with presence and severity of cancer treatment-related side effects and symptoms and also influence the response to exercise-based interventions in cancer survivors.”
DOI: https://doi.org/10.18632/oncotarget.28310
Correspondence to: Jacob Raber - raberj@ohsu.edu
Video: https://www.youtube.com/watch?v=CvN9ZDWymz8
Keywords: apoE, breast cancer, exercise intervention, fall rate, functional status
About Oncotarget:
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com
A new research paper was published in Oncotarget’s Volume 13 on November 17, 2022, entitled, “Mutation analysis performed on tumor biopsies from patients with newly-diagnosed germinal center aggressive B cell lymphomas.”
Comprehensive genomic analyses of tumor biopsies from patients with newly-diagnosed germinal center B cell (GCB) diffuse large B cell/high grade B cell lymphoma (DLBCL/HGBL) have identified molecular subtypes predictive of inferior survival, which are characterized by somatic mutations that can be detected through clinical laboratory mutation analysis (CLMA).
To determine the frequency and predictive value of individual genetic mutations associated with these experimentally-defined poor-risk subgroups, researchers Daniel J. Landsburg, Jennifer J.D. Morrissette, Stephen J. Schuster, Sunita D. Nasta, James N. Gerson, Stefan K. Barta, Jakub Svoboda, Elise A. Chong, and Megan S. Lim from the University of Pennsylvania reviewed the findings from CLMA performed on tumors from patients with newly-diagnosed GCB DLBCL/HGBL who were previously treated at the University of Pennsylvania.
“Thus, we sought to analyze the results of CLMA performed at our institution on tumors from patients with newly-diagnosed GCB DLBCL/HGBL previously-treated with first line immunochemotherapy to determine the frequency and predictive value of the presence of individual genetic mutations associated with these experimentally-defined poor-risk subgroups.”
CLMA was successfully performed on 58/59 patient tumor biopsies with a median turnaround time of 16 days, and 51 on which CLMA was routinely performed with adequate clinical follow-up were analyzed. Patients whose tumors demonstrated CREBBP mutation experienced a lower estimated rate of 2-year disease free survival (DFS) as compared to those whose tumors did not (45% [95% CI 18–68%] vs. 67% [95% CI 44–83%], P = 0.045). The researchers note that CREBBP mutations may be frequent and predict for inferior DFS in patients with newly-diagnosed GCB DLBCL/HGBL. Furthermore, CLMA may be practically-applied to translate experimental findings into those with more direct application to risk stratification and clinical trial design in subsets of patients with DLBCL/HGBL.
“In conclusion, CLMA performed on tumor biopsies from patients with newly-diagnosed GCB DLBCL/HGBL revealed frequent mutations in CREBBP which were predicted to result in loss of function as well as a significantly lower rate of estimated DFS at 2 years.”
DOI: https://doi.org/10.18632/oncotarget.28309
Correspondence to: Daniel J. Landsburg
Email: daniel.landsburg@pennmedicine.upenn.edu
Video: https://www.youtube.com/watch?v=yqTQOv8Vufc
Keywords: diffuse large B cell lymphoma, high grade B cell lymphoma, mutation analysis, next generation sequencing, chemotherapy
About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com.
Listen to a blog summary of a research paper published in Volume 13, entitled, "Predictive molecular biomarkers for determining neoadjuvant chemosensitivity in muscle invasive bladder cancer." _______________________________________________
Neoadjuvant chemotherapy (NAC) is a type of cancer treatment involving the administration of chemotherapy drugs before surgery. The goal of NAC is to shrink the tumor(s) in order to make it/them easier to remove during surgery and to decrease the chance of cancer recurrence after treatment. NAC is typically well tolerated by patients and has been shown to improve outcomes in patients with bladder cancer.
Predictive biomarkers are being increasingly used in oncology to identify patients who are likely to respond to chemotherapy. In the past, the decision to administer chemotherapy was based on tumor type and stage. However, it is now understood that there is considerable heterogeneity within these groups, and that not all patients will respond to the same treatment. Predictive biomarkers can help to overcome this challenge by identifying those patients who are most likely to benefit from chemotherapy.
There are a number of different types of predictive biomarkers, which can be divided into two broad categories: tumor biomarkers and host biomarkers. Tumor biomarkers are usually specific to the tumor type and can include markers of cell proliferation and DNA repair. Host biomarkers are usually found in the blood or other bodily fluids and can include markers of inflammation, immune function and metabolism. The use of predictive biomarkers has the potential to improve the efficacy of chemotherapy and reduce toxicity by avoiding its use in patients who are unlikely to benefit.
In a new study, researchers Neal Murphy, Andrew J. Shih, Paras Shah, Oksana Yaskiv, Houman Khalili, Anthony Liew, Annette T. Lee, and Xin-Hua Zhu from Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health Cancer Institute, Feinstein Institutes for Medical Research, and Mayo Clinic aimed to develop and validate a predictive biomarker panel for response to NAC in patients with muscle-invasive bladder cancer (MIBC). Their research paper was published on November 2, 2022, in Oncotarget’s Volume 13, entitled, “Predictive molecular biomarkers for determining neoadjuvant chemosensitivity in muscle invasive bladder cancer.”
Full blog - https://www.oncotarget.org/2022/11/15/biomarkers-may-predict-neoadjuvant-chemosensitivity-in-bladder-cancer/
DOI - https://doi.org/10.18632/oncotarget.28302
Correspondence to - Neal Murphy - nmurphy2@northwell.edu, Annette T. Lee - alee@northwell.edu, and Xin-Hua Zhu - xzhu1@northwell.edu
Press release - https://www.oncotarget.com/index.php?journal=oncotarget&page=news&op=press&item=oncotarget-predictive-molecular-biomarkers-for-determining-neoadjuvant-chemosensitivity-in-muscle-invasive-bladder-cancer
Keywords - muscle invasive bladder cancer, neoadjuvant chemotherapy, gene expression, molecular subtyping, canonical correlation analysis
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
A new research paper was published in Oncotarget’s Volume 13 on November 2, 2022, entitled, “MK256 is a novel CDK8 inhibitor with potent antitumor activity in AML through downregulation of the STAT pathway.”
Acute myeloid leukemia (AML) is the most lethal form of AML due to disease relapse. Cyclin dependent kinase 8 (CDK8) is a serine/threonine kinase that belongs to the family of Cyclin-dependent kinases and is an emerging target for the treatment of AML. MK256, a potent, selective, and orally available CDK8 inhibitor was developed to target AML.
In this new study, researchers Jen-Chieh Lee, Shu Liu, Yucheng Wang, You Liang, and David M. Jablons from the University of California San Francisco and Touro University sought to examine the anticancer effect of MK256 on AML.
“In CD34+/CD38- leukemia stem cells, we found that MK256 induced differentiation and maturation.”
Treatment of MK256 inhibited proliferation of AML cell lines. Further studies of the inhibitory effect suggested that MK256 not only downregulated phosphorylated STAT1(S727) and STAT5(S726), but also lowered mRNA expressions of MCL-1 and CCL2 in AML cell lines. Efficacy of MK256 was shown in MOLM-14 xenograft models, and the inhibitory effect on phosphorylated STAT1(S727) and STAT5(S726) with treatment of MK256 was observed in vivo.
Pharmacologic dynamics study of MK256 in MOLM-14 xenograft models showed dose-dependent inhibition of the STAT pathway. Both in vitro and in vivo studies suggested that MK256 could effectively downregulate the STAT pathway. In vitro ADME, pharmacological kinetics, and toxicity of MK256 were profiled to evaluate the drug properties of MK256.
“Our results show that MK256 is a novel CDK8 inhibitor with a desirable efficacy and safety profile and has great potential to be a promising drug candidate for AML through regulating the STAT pathway.”
DOI: https://doi.org/10.18632/oncotarget.28305
Correspondence to: Jen-Chieh Lee -jenchieh.lee@ucsf.edu, Shu Liu - shu.liu@ucsf.edu
Keywords: AML, CDK8, kinase inhibitor, STAT pathway, xenograft
Video: https://www.youtube.com/watch?v=8bRgqTg9-c8
About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com
A new research paper was published in Oncotarget's Volume 13 on October 20, 2022, entitled, “Nectin-4 is widely expressed in head and neck squamous cell carcinoma.”
Nectin-4 has been successfully established as a target molecule in locally advanced and metastatic bladder cancer. An antibody-drug conjugate (enfortumab-vedotin) directed against nectin-4 has shown marked tumor remission rates in this tumor type, which is known for high expression rates of nectin-4.
As head and neck cancer and urothelial carcinomas share morphological and molecular similarities, researchers Christine Sanders, Jan-Frederic Lau, Dimo Dietrich, Sebastian Strieth, Peter Brossart, and Glen Kristiansen from University Medical Center Bonn and University Hospital Bonn aimed to evaluate Nectin-4 expression in head and neck squamous cell carcinoma (HNSCC).
A previously described and clinically characterized cohort of HNSCC (n = 159) was analyzed by immunohistochemistry for Nectin-4 expression. The expression data was correlated to clinico-pathological parameters including patient outcome.
Nectin-4 was found in 86.2% of HNSCC, with medium/high expression seen in 32.7% of cases. Non smokers and p16 positive HNSCC showed a higher expression of Nectin-4 (p < 0.005). There was no correlation of Nectin-4 with grading or tumor stage. Nectin-4 positive tumors showed significantly better survival (log rank p = 0.006).
“Similar to urothelial carcinoma, Nectin-4 is found in the majority of HNSCC, which clearly warrants further studies to clarify if HNSCC also respond to targeted therapy with enfortumab-vedotin. Moreover, expression of Nectin-4 is associated with HPV infection and may serve as a prognostic marker in HNSCC.”
DOI: https://doi.org/10.18632/oncotarget.28299
Correspondence to: Glen Kristiansen - Email: glen.kristiansen@ukbonn.de
Video - https://www.youtube.com/watch?v=tDY21YpFsKc
Keywords: Nectin-4, enfortumab-vedotin, HNSCC, p16
About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com
Oncotarget Journal Office 6666 East Quaker Str., Suite 1A Orchard Park, NY 14127 Phone: 1-800-922-0957 (option 2)
Listen to a blog summary about a research perspective published in Volume 13 of Oncotarget, entiutled, "FSP1, a novel KEAP1/NRF2 target gene regulating ferroptosis and radioresistance in lung cancers." __________________________________________________
Ferroptosis is a type of cell death caused by the accumulation of iron and lipid peroxides in cells. Cancer cells are often resistant to ferroptosis, which allows them to survive and proliferate. Radioresistance is another common feature of cancer cells that allows them to resist the effects of radiation therapy.
A new research paper (published on April 22, 2022) identified ferroptosis suppressor protein 1 (FSP1) as a novel KEAP1/NRF2 target gene and demonstrated that FSP1 plays an essential role in NRF2-mediated ferroptosis resistance and radioresistance in KEAP1-deficient lung cancer cells.
Recently, researchers Nsengiyumva Emmanuel, Hongen Li, Jing Chen, and Yilei Zhang from Xi’an Jiaotong University, Ruyang People’s Hospital and Shaanxi Jiuzhou Biomedical Science and Technology Group wrote a paper about the implications of these findings. On October 19, 2022, their research perspective was published in Oncotarget’s Volume 13, entitled, “FSP1, a novel KEAP1/NRF2 target gene regulating ferroptosis and radioresistance in lung cancers.”
“In a recent study by Pranavi Koppula et al. from The University of Texas MD Anderson Cancer Center, FSP1 was demonstrated as a novel target of NRF2 and to play a vital role in KEAP1/NRF2-mediated ferroptosis regulation [13], which reveals the important role of genetic regulation of FSP1 in cancer development.”
Full blog - https://www.oncotarget.org/2022/11/02/new-target-fights-ferroptosis-and-radio-resistance-in-lung-cancers/
DOI - https://doi.org/10.18632/oncotarget.28301
Correspondence to - Yilei Zhang - zhangyilei@xjtu.edu.cn
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28301
Keywords - KEAP1/NRF2, lung cancer, ferroptosis, radioresistance, therapy
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
BUFFALO, NY- October 27, 2022 – On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by MEDLINE/PubMed and PubMed Central/PubMed.
The United States government is firmly committed to making credible biomedical research available to the public. In operation since 1996, PubMed is an online biomedical literature database operated by the U.S. National Institutes of Health (NIH). PubMed provides free access to over 34 million citations from MEDLINE, PubMed Central (PMC) and the National Center for Biotechnology Information databases.
Started back in the 1960s, MEDLINE is a large bibliographic citation and abstract database for life science articles in journals and other scientific publications. MEDLINE now contains more than 29 million references to articles in over 5,200 journals. In 2000, PMC was launched as a free, full-text archive of biomedical and life sciences journal literature.
Both MEDLINE and PMC are operated by the NIH’s National Library of Medicine. Importantly, PubMed and MEDLINE use the same controlled vocabulary thesaurus, called Medical Subject Headings, or MeSH, to ensure that content is easily searchable and properly indexed. The vast scope of scholarly publications in MEDLINE is why Oncotarget is proud to have its papers indexed by this database.
Oncotarget, launched in 2010, is a peer-reviewed, open-access and primarily oncology-focused biomedical journal. This journal has international reach—publishing research from world-renowned institutions. The cornerstones of Oncotarget’s publishing practices are insightful peer review, scientific integrity, rigorous ethical standards, up-to-date tools and resources, and a commitment to local and scientific communities. Oncotarget aims to maximize research impact, eliminate borders between specialties and foster the application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget
For media inquiries, please contact media@impactjournals.com
A new research paper was published in Oncotarget's Volume 13 on October 19, 2022, entitled, “Therapeutic efficacy of the humanized JAA-F11 anti-Thomsen-Friedenreich antibody constructs H2aL2a and H3L3 in human breast and lung cancer xenograft models.”
The Thomsen-Friedenreich antigen (TF-Ag-α) is found on ~85% of human carcinomas but is cryptic on normal tissue. The humanized, highly specific hJAA-F11-H2aL2a and -H3L3 antibodies target TF-Ag-α without binding to TF-Ag-beta (found on surface glycolipids of some normal cells).
“The relative affinity of H3L3 is 17 times that of H2aL2a, which would seem to favor superior efficacy, however, increased affinity can result in less tumor penetration.”
In a new study, researchers Diala Ghazal, Fatma Zalzala, John C. Fisk, Swetha Tati, Loukia G. Karacosta, Susan Morey, James R. Olson, Sally Quataert, Grace K. Dy, and Kate Rittenhouse-Olson from For-Robin, Inc, University at Buffalo, University of Rochester, and Roswell Park Comprehensive Cancer Center Buffalo aimed to assess the potential therapeutic efficacy of these antibodies by treating four human cancer- mouse xenograft models with H2aL2a and H3L3. The tumor xenograft models used were human non-small cell lung cancer, H520, and small cell lung cancer, HTB171 in nude mice and human triple negative breast cancer, MDA-MB-231 and HCC1806 in SCID mice.
H2aL2a significantly decreased tumor growth in both breast and both lung cancer models. H2aL2a showed statistically equal or better efficacy than H3L3 and has superior production capabilities. These results suggest that H2aL2a may be superior as a naked antibody, as an antibody drug conjugate or as a radiolabeled antibody, however the higher affinity of H3L3 may lead to better efficacy in bi-specific therapies in which the binding is decreased due to the presence of only one TF-Ag-α binding site.
“In conclusion, both H2aL2a and H3L3 humanized antibodies to TF-Ag-α show efficacy in in vivo xenograft models of human tumors in SCID and nude mice and thus hold promise as therapeutics for breast and lung cancer. H2aL2a significantly decreased tumor growth rate in both breast cancer and both lung cancer models tested. H2aL2a is equal to or better than H3L3 in four of the four models and H2aL2a cell lines have far superior antibody production capabilities under the conditions tested.”
DOI: https://doi.org/10.18632/oncotarget.28282
Correspondence to: Kate Rittenhouse-Olson - krolson@buffalo.edu
Keywords: hJAA-F11, TF-Ag, Thomsen-Friedenreich antigen, tumor immunotherapy, translational oncology
About Oncotarget:
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OA SoundCloud - https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com.
Oncotarget Journal Office
6666 East Quaker Str., Suite 1A Orchard Park, NY 14127 Phone: 1-800-922-0957 (option 2)
A new research paper was published in Oncotarget's Volume 13 on October 19, 2022, entitled, “Platelet-derived growth factor (PDGF) cross-signaling via non-corresponding receptors indicates bypassed signaling in colorectal cancer.”
Platelet-derived growth factor (PDGF) signaling, besides other growth factor-mediated signaling pathways like vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), seems to play a crucial role in tumor development and progression.
Previously, researchers Romana Moench, Martin Gasser, Karol Nawalaniec, Tanja Grimmig, Amrendra K. Ajay, Larissa Camila Ribeiro de Souza, Minghua Cao, Yueming Luo, Petra Hoegger, Carmen M. Ribas, Jurandir M. Ribas-Filho, Osvaldo Malafaia, Reinhard Lissner, Li-Li Hsiao, and Ana Maria Waaga-Gasser, from Harvard Medical School, Shenzhen Traditional Chinese Medicine Hospital, University of Wuerzburg, and Mackenzie Evangelical Faculty of Paraná, recently provided evidence for upregulation of PDGF expression in UICC stage I–IV primary colorectal cancer (CRC) and demonstrated PDGF-mediated induction of PI3K/Akt/mTOR signaling in CRC cell lines. In their new study, the researchers sought to follow up on our previous findings and explore the alternative receptor cross-binding potential of PDGF in CRC.
“Our analysis of primary human colon tumor samples demonstrated upregulation of the PDGFRβ, VEGFR1, and VEGFR2 genes in UICC stage I-III tumors.”
Immunohistological analysis revealed co-expression of PDGF and its putative cross-binding partners, VEGFR2 and EGFR. The team then analyzed several CRC cell lines for PDGFRα, PDGFRβ, VEGFR1, and VEGFR2 protein expression. They found these receptors to be variably expressed amongst the investigated cell lines.
Interestingly, whereas Caco-2 and SW480 cells showed expression of all analyzed receptors, HT29 cells expressed only VEGFR1 and VEGFR2. However, stimulation of HT29 cells with PDGF resulted in upregulation of VEGFR1 and VEGFR2 expression despite the absence of PDGFR expression and mimicked the effect of VEGF stimulation. Moreover, PDGF recovered HT29 cell proliferation under simultaneous treatment with a VEGFR or EGFR inhibitor.
“Our results provide some of the first evidence for PDGF cross-signaling through alternative receptors in colorectal cancer and support anti-PDGF therapy as a combination strategy alongside VEGF and EGF targeting even in tumors lacking PDGFR expression.”
DOI: https://doi.org/10.18632/oncotarget.28281
Correspondence to: Ana Maria Waaga-Gasser - awaaga@bwh.harvard.edu
Keywords: PDGF, VEGFR, EGFR, bypassed signaling, colorectal cancer
About Oncotarget:
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OA SoundCloud - https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com.
Oncotarget Journal Office 6666 East Quaker Str., Suite 1A Orchard Park, NY 14127 Phone: 1-800-922-0957 (option 2)
Listen to a blog summary of a recently published research paper in Volume 13 of Oncotarget, entitled, "HDAC inhibitors suppress protein poly(ADP-ribosyl)ation and DNA repair protein levels and phosphorylation status in hematologic cancer cells: implications for their use in combination with PARP inhibitors and chemotherapeutic drugs." _______________________________________
Chromatin constitutes chromosomes in eukaryotic cells and comprises DNA and proteins. Chromosomes produce proteins and enzymes that are essential for cellular function and maintenance, including DNA repair. A critical process for DNA repair is poly(ADP-ribosyl)ation, or PARylation.
PARylation is triggered by poly(ADP ribose) polymerase (PARP) enzymes. When DNA becomes damaged, PARP enzymes bind to the damaged location in the cell. In cancer cells, however, this natural process can be counterproductive in respect to cancer treatment. PARylation can produce DNA repair mechanisms in cancer cells that can lead to the evasion of cell death, and even drug resistance. Inhibiting PARylation may be a viable therapeutic strategy for cancer treatment.
Histones, the main proteins that constitute chromatin, undergo post-translational modifications that regulate gene expression. Histone acetylation is an important epigenetic process that affects gene expression by relaxing the chromatin structure, making chromatin remodeling more feasible. Histone deacetylases (HDACs) are enzymes that can have the opposite effect. Histone deacetylation makes the chromatin more compact and difficult to remodel. The overexpression of HDAC has also been associated with tumorigenesis. Histone deacetylase inhibitors (HDACi) are a class of therapeutics that have shown promise in the treatment of hematologic malignancies (blood cancer) and solid tumors.
In a new study, researchers Benigno C. Valdez, Yago Nieto, Bin Yuan, David Murray, and Borje S. Andersson from the Department of Stem Cell Transplantation and Cellular Therapy at the University of Texas MD Anderson Cancer Center and the Cross Cancer Institute’s Department of Experimental Oncology at the University of Alberta investigate the efficacy of HDACi in combination with PARP inhibitors (PARPi) and chemotherapeutic drugs to treat hematologic cancer. On October 14, 2022, their research paper was published in Volume 13 of Oncotarget, entitled, “HDAC inhibitors suppress protein poly(ADP-ribosyl)ation and DNA repair protein levels and phosphorylation status in hematologic cancer cells: implications for their use in combination with PARP inhibitors and chemotherapeutic drugs.”
Full blog - https://www.oncotarget.org/2022/10/19/synergy-of-hdaci-parpi-and-chemotherapeutics-against-blood-cancer/
DOI - https://doi.org/10.18632/oncotarget.28278
Correspondence to - Benigno C. Valdez - bvaldez@mdanderson.org
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28278
Keywords - poly(ADP-ribosyl)ation, HDAC inhibitors, PARP inhibitors, chemotherapy, hematologic malignancy
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new research paper was published in Oncotarget's Volume 13 on October 8, 2022, entitled, “Effectiveness of radiotherapy for local control in T3N0 rectal cancer managed with total mesorectal excision: a meta-analysis.”
The total mesorectal excision (TME) significantly improves rectal cancer outcomes. Radiotherapy’s benefit in T3N0 rectal cancer patients managed with TME has not been clearly demonstrated.
In a new study, researchers Michael Jonathan Kucharczyk, Andrew Bang, Michael C. Tjong, Stefania Papatheodoru, and Jesus C. Fabregas from Nova Scotia Cancer Centre, Dalhousie University, BC Cancer – Vancouver, Princess Margaret Cancer Centre, Harvard T.H. Chan School of Public Health, and University of Florida Health Cancer Center conducted a systematic review and meta-analysis to determine whether radiotherapy alteres the risk of locoregional recurrence (LR) in T3N0 rectal cancer patients managed with a TME.
“This systematic review identified unique 7 retrospective cohort studies which evaluated whether radiotherapy reduces LR in T3N0 rectal cancer patients managed with TME.”
The studies indexed on PubMed or Embase were systematically searched from inception to October 18, 2020. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were observed for the literature search, study screening and data extraction; the Newcastle Ottawa Scale evaluated bias; Grades of Recommendation, Assessment, Development, and Evaluation Working Group system evaluated certainty. All were performed independently by at least two investigators.
Studies that reported LR data specific to T3N0 rectal cancer patients managed with TME, treated with and without radiotherapy, were included. Data was pooled using a random-effects model. Meta-analyses of the relative risk of local recurrence were conducted.
Five retrospective cohort studies involving 932 unique patients reported LR outcomes; no prospective studies met eligibility criteria. Median follow-up ranged from 38.4–78 months. Adjuvant radiotherapy was provided in 3 studies. Chemotherapy was delivered and reported in 4 studies, providing both concurrent and adjuvant chemotherapy.
A non-significant LR benefit with radiotherapy’s addition was estimated. Meta-analysis of exclusively retrospective cohort studies was concerning for biased results. Adequately powered randomized trials are warranted.
“With low certainty, this meta-analysis observed a non-significant benefit with radiotherapy to 5-year LR rates among T3N0 rectal cancer patients that received a TME. Until a pragmatically sized randomized control trial is completed, our research adds a layer of data to facilitate informed and personalized treatment decisions for T3N0 rectal cancer patients, albeit with potential significant bias from solely relying on retrospective cohort studies.”
DOI: https://doi.org/10.18632/oncotarget.28280
Correspondence to: Michael Jonathan Kucharczyk - michael.kucharczyk@medportal.ca
Keywords: radiotherapy, meta-analysis, systematic review, rectal cancer, total mesorectal excision
About Oncotarget:
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OA SoundCloud - https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com.
A new research paper was published in Oncotarget’s Volume 13 on October 8, 2022, entitled, “In vitro chemotherapy-associated muscle toxicity is attenuated with nutritional support, while treatment efficacy is retained.”
Muscle-wasting and treatment-related toxicities negatively impact prognosis of colorectal cancer (CRC) patients. Specific nutritional composition might support skeletal muscle and enhance treatment support.
In this new in vitro study, researchers Liza A. Wijler, Francina J. Dijk, Hanil Quirindongo, Danielle A.E. Raats, Bram Dorresteijn, Matthew J.W. Furber, Anne M. May, Onno Kranenburg, and Miriam van Dijk, from University Medical Centre Utrecht, Danone Nutricia Research and Utrecht University, assessed the effect of nutrients eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), L-leucine, and vitamin D3 as single nutrients or in combination on chemotherapy-treated C2C12-myotubes and specific CRC-tumor cells.
Using C2C12-myotubes, the effects of chemotherapy (oxaliplatin, 5-fluorouracil, oxaliplatin+5-fluorouracil and irinotecan) on protein synthesis, cell-viability, caspase-3/7-activity and lactic acid dehydrogenase (LDH)-activity were assessed. Addition of EPA, DHA, L-leucine and vitamin D3 and their combination (SNCi) were studied in presence of above chemotherapies. Tumor cell-viability was assessed in oxaliplatin-treated C26 and MC38 CRC cells, and in murine and patient-derived CRC-organoids.
While chemotherapy treatment of C2C12-myotubes decreased protein synthesis, cell-viability and increased caspase-3/7 and LDH-activity, SNCi showed improved protein synthesis and cell viability and lowered LDH activity. The nutrient combination SNCi showed a better overall performance compared to the single nutrients. Treatment response of tumor models was not significantly affected by addition of nutrients.
“This in vitro study shows protective effect with specific nutrition composition of C2C12-myotubes against chemotherapy toxicity, which is superior to the single nutrients, while treatment response of tumor cells remained.”
DOI: https://doi.org/10.18632/oncotarget.28279
Correspondence to: Miriam van Dijk – Email: miriam.vandijk@danone.com
Keywords: C2C12 myotubes, chemotherapy, chemotherapy-associated toxicity, colorectal cancer, nutrients, tumor (organoid) cells
About Oncotarget:
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com
Blog summary of a trending research paper published by Oncotarget, entitled, "Complementary CRISPR genome-wide genetic screens in PARP10-knockout and overexpressing cells identify synthetic interactions for PARP10-mediated cellular survival." _________________________________________
Genetic interactions involved in the survival of cancer cells are potential therapeutic targets in personalized cancer therapy. “Synthetic lethal” is a type of genetic interaction where the knockout of one gene can cause cell death but only in the presence of another dependent gene. Cancer researchers view synthetic lethality screening as a powerful tool in precision medicine.
“Identifying genetic susceptibilities based on PARP10 expression levels is thus potentially relevant for finding new targets for precision oncology.”
Poly-ADP-ribose polymerase 10, or PARP10, is a nuclear protein that is overexpressed in multiple cancers. Genetic susceptibilities based on PARP10 expression levels in an individual may be potential targets for personalized cancer therapy. In a new study, researchers Jude B. Khatib, Emily M. Schleicher, Lindsey M. Jackson, Ashna Dhoonmoon, George-Lucian Moldovan, and Claudia M. Nicolae, from the Department of Biochemistry and Molecular Biology at Penn State College of Medicine, used CRISPR-based, genome-wide genetic screens to identify potential synthetic lethality interactions with PARP10-overexpressing and -knockout cancer cells. On September 28, 2022, their research paper was published in Oncotarget and entitled, “Complementary CRISPR genome-wide genetic screens in PARP10-knockout and overexpressing cells identify synthetic interactions for PARP10-mediated cellular survival.”
“Here, we employed complementary CRISPR loss-of-function genome-wide screening to identify genes required for proliferation of PARP10-overexpressing and PARP10-knockout cells.”
Full blog - https://www.oncotarget.org/2022/10/07/crispr-screens-identify-novel-targets-for-personalized-cancer-therapy/
DOI - https://doi.org/10.18632/oncotarget.28277
Correspondence to - Claudia M. Nicolae - cmn14@psu.edu
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28277
Keywords - PARP10, ATM, CRISPR screens, genome stability, cancer cell proliferation
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new research paper was published in Oncotarget's Volume 13 on September 28, 2022, entitled, “Genomic alterations predictive of poor clinical outcomes in pan-cancer.”
Genomic alterations are highly frequent across cancers, but their prognostic impact is not well characterized in pan-cancer cohorts.
In this new study, researchers Crystal S. Seldon, Karthik Meiyappan, Hannah Hoffman, Jimmy A. Guo, Neha Goel, William L. Hwang, Paul L. Nguyen, Brandon A. Mahal, and Mohammed Alshalalfa from the University of Miami, Massachusetts General Hospital, Broad Institute of MIT, University of California San Francisco, and Dana-Farber Cancer Institute and Brigham and Women’s Hospital used pan-cancer cohorts from The Cancer Genome Atlas (TCGA) and the MSK-IMPACT study to evaluate the associations of common genomic alterations with poor clinical outcome.
“There is growing interest in genomic profiling (i.e. tumor mutations, copy number (CN) alterations) for cancer therapy and precision oncology to inform treatment decisions and identify patients for relevant clinical trials [1].”
Full press release - https://www.oncotarget.net/2022/10/04/oncotarget-genomic-alterations-predictive-of-poor-clinical-outcomes-in-pan-cancer/
DOI: https://doi.org/10.18632/oncotarget.28276
Correspondence to: Mohammed Alshalalfa - mohamed.alshalalfa@gmail.com
Keywords: genomic alterations, TP53, TCGA, poor prognosis
About Oncotarget:
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OA SoundCloud - https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com
A new research paper was published in Oncotarget’s Volume 13 on September 14, 2022, entitled, “Site of analysis matters – Ongoing complete response to Nivolumab in a patient with HIV/HPV related metastatic anal cancer and MLH1 mutation.”
Anal cancer is a rare disease with increasing incidence. In patients with locally recurrent or metastatic disease, which cannot be treated with chemoradiotherapy or salvage surgery, systemic first-line chemotherapy with carboplatin and paclitaxel is standard of care. For patients who progress after first-line therapy and are still eligible for second-line therapy, programmed cell death protein 1 (PD-1) antibodies are potential therapeutic options. However, prediction of response to immunotherapy is still challenging, including in patients with anal cancer.
“Altogether, there is little data on PD-1 treatment in HIV infected patients.”
In a new study, researchers Melanie Demes, Ursula Pession, Jan Jeroch, Falko Schulze, Katrin Eichler, Daniel Martin, Peter Wild, and Oliver Waidmann from Universitätsklinikum Frankfurt and Centrum für Hämatologie und Onkologie reported a case of an HIV infected patient with anal cancer, microsatellite instability (MSI) high status, a high mutation frequency regarding tumor mutational burden (TMB) and an ongoing response to Nivolumab.
“We report here to our knowledge the first anal cancer case with microsatellite instability (MSI) due to MLH1 mutation and a deep and ongoing response to Nivolumab treatment.”
Thorough analysis of the primary tumor as well as metastatic sites by next generation sequencing (NGS) revealed that MSI was formally only found in the metastatic sites but not in the primary tumor. Concomitantly, tumor mutational burden (TMB) was higher in the metastatic site than in the primary tumor. The researchers concluded that all anal cancer patients should be tested for MSI and whenever possible molecular analysis should be performed rather from metastatic sites than from the primary tumor.
“According to our results, we propose to assess mutational status in tissue from metastasis rather than from the primary site when additional molecular analyses are performed for treatment decisions.”
DOI: https://doi.org/10.18632/oncotarget.28274
Correspondence to: Oliver Waidmann – Emails: oliver.waidmann@kgu.de
Keywords: anal cancer, microsatellite instability, immunotherapy, high-throughput nucleotide sequencing, nivolumab
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Blog summary of a research paper recently published by Oncotarget, entitled, "Influence of high altitude on the expression of HIF-1 and on the prognosis of Ecuadorian patients with gastric adenocarcinoma." _____________________________________
Altitude is considered any elevation above sea level. Higher altitude environments are known to influence various physiological processes in the human body, including those related to hypoxia-inducing factors (HIF), vitamin D, ultraviolet radiation, oxygen toxicity, and changes in pH. Researchers have suggested that altitude may even affect the development and progression of some diseases, including stomach/gastric cancer.
“Gastric cancer is the third leading cause of death in the world and is estimated to cause almost 15 million deaths by 2035 [2].”
Gastric Cancer & Altitude
The primary subtype of gastric cancer is gastric adenocarcinoma (GA). GA develops in the mucus-secreting cells that line the stomach (gastric epithelium). Higher incidence rates of GA have been found among populations living at high altitudes. High altitudes are notorious for low air pressure and decreased oxygen saturation levels. Decreases in oxygen (hypoxia) can activate the transcriptional regulator hypoxia-inducing factor-1 (HIF-1). HIF-1 is known to be upregulated in a variety of human cancers, including GA. The role of HIF-1 in GA pathogenesis and prognosis has not yet been fully understood.
“Gastric adenocarcinoma (GA) has a high incidence in Ecuador, in men it ranks third and in women it ranks fifth.”
There is a higher incidence of GA among people living in Ecuador. This is a country that straddles the equator yet, the altitude in Ecuador varies significantly across the country. For example, the altitude is 2,850 meters in the capital city of Quito (the second-highest capital city in the world). In Guayaquil (a coastal city in Ecuador) the altitude is only nine meters. These facts make Ecuador an optimal location for studying the effects of altitude on gastric adenocarcinoma.
“Ecuador has a varied altitude diversity and there is a differential incidence of cancer between populations living in the Andean or mountainous region when compared to coastal populations or living at low altitude.”
Full blog - https://www.oncotarget.org/2022/09/27/how-high-altitudes-influence-hif-1-gastric-cancer-patient-survival/
DOI - https://doi.org/10.18632/oncotarget.28275
Correspondence to - José Sebastiao dos Santos - lab.biomol.cirugia@fmrp.usp.br
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28275
Keywords - cancer, gastric adenocarcinoma, hypoxia-induced factor, HER2, survival rate, tumor markers
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to a blog summary of a trending research paper published by Oncotarget, entitled, "Prediction of recurrence free survival for esophageal cancer patients using a protein signature based risk model." _________________________________________
Esophageal cancer is the sixth most common cause of death from cancer worldwide. The two main types of esophageal cancer are adenocarcinoma and esophageal squamous cell carcinoma (ESCC). ESCC arises from the cells lining the esophagus, and it is most common in areas of the world where tobacco use and alcohol consumption are high.
“Biomarkers to predict the risk of disease recurrence in Esophageal squamous cell carcinoma (ESCC) patients are urgently needed to improve treatment.”
Researchers Raghibul Hasan, Gunjan Srivastava, Akram Alyass, Rinu Sharma, Anoop Saraya, Tushar K. Chattopadhyay, Siddartha DattaGupta, Paul G. Walfish, Shyam S. Chauhan, and Ranju Ralhan from All India Institute of Medical Sciences, Mount Sinai Hospital Toronto, McMaster University, Guru Gobind Singh Indraprastha University, and the University of Toronto conducted a new study on the protein expression-based risk model they developed to predict recurrence-free survival for ESCC patients. On September 14, 2022, their research paper was published in Oncotarget’s Volume 13, and entitled, “Prediction of recurrence free survival for esophageal cancer patients using a protein signature based risk model.”
“Our study is important because: (i) it is based on changes in expression levels of the biomarker proteins in different subcellular compartments and is not limited to alterations in the overall protein expression levels; (ii) investigates the comprehensive clinical relevance of subcellular alterations in expression of multiple key components of Wnt pathway in the same ESCC patients’ cohort; (iii) correlates these findings with disease outcome and (iv) develops a Biomarker risk score for defining the risk of recurrence of ESCCs.”
Full blog - https://www.oncotarget.org/2022/09/23/protein-based-risk-model-predicts-esophageal-cancer-recurrence/
DOI - https://doi.org/10.18632/oncotarget.10656
Correspondence to - Ranju Ralhan - rralhan@mtsinai.on.ca, Shyam S. Chauhan - s_s_chauhan@hotmail.com
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.10656
Keywords - esophageal cancer, wnt proteins, disheveled, molecular markers, prognosis
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
BUFFALO, NY- September 20, 2022 – A new research paper was published in Oncotarget’s Volume 13 on September 14, 2022, entitled, “Targeting Krebs-cycle-deficient renal cell carcinoma with Poly ADP-ribose polymerase inhibitors and low-dose alkylating chemotherapy.”
Loss-of-function mutations in genes encoding the Krebs cycle enzymes Fumarate Hydratase (FH) and Succinate Dehydrogenase (SDH) induce accumulation of fumarate and succinate, respectively, and predispose patients to hereditary cancer syndromes including the development of aggressive renal cell carcinoma (RCC).
Fumarate and succinate competitively inhibit αKG-dependent dioxygenases, including Lysine-specific demethylase 4A/B (KDM4A/B), leading to suppression of the homologous recombination (HR) DNA repair pathway.
Researchers Daiki Ueno, Juan C. Vasquez, Amrita Sule, Jiayu Liang, Jinny van Doorn, Ranjini Sundaram, Sam Friedman, Randy Caliliw, Shinji Ohtake, Xun Bao, Jing Li, Huihui Ye, Karla Boyd, Rong Rong Huang, Jack Dodson, Paul Boutros, Ranjit S. Bindra, and Brian Shuch from Yale University School of Medicine, West China Hospital/School of Medicine, Wayne State University, and University of California, Los Angeles have developed new syngeneic Fh1- and Sdhb-deficient murine models of RCC, which demonstrate the expected accumulation of fumarate and succinate, alterations in the transcriptomic and methylation profile, and an increase in unresolved DNA double-strand breaks (DSBs).
“In this study, we sought to examine the activity of combined TMZ and PARPi in Krebs-cycle-deficient renal cancer models. Fh1 and Sdhb are the murine counter part of human FH and SDHB, respectively.”
The efficacy of poly ADP-ribose polymerase inhibitors (PARPis) and temozolomide (TMZ), alone and in combination, was evaluated both in vitro and in vivo. Combination treatment with PARPi and TMZ results in marked in vitro cytotoxicity in Fh1- and Sdhb-deficient cells. In vivo, treatment with standard dosing of the PARP inhibitor BGB-290 and low-dose TMZ significantly inhibits tumor growth without a significant increase in toxicity.
These findings provide the basis for a novel therapeutic strategy exploiting HR deficiency in FH and SDH-deficient RCC with combined PARP inhibition and low-dose alkylating chemotherapy.
“Using newly developed Fh1 and Sdhb deficient syngeneic mouse models, we demonstrate that oncometabolite-induced HR defects can be leveraged with PARPi treatment to enhance sensitivity to low-dose TMZ in Krebs-cycle-deficient renal cancer.”
DOI: https://doi.org/10.18632/oncotarget.28273
Correspondence to: Ranjit S. Bindra & Brian Shuch – Emails: Ranjit.Bindra@yale.edu & bshuch@mednet.ucla.edu
Keywords: FH, SDHB, renal cell carcinoma, PARP inhibitor, temozolomide
About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com.
Dr. Balraj Singh from the Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, describes a recent research paper he co-authored that was published by Oncotarget, entitled, “Inhibition of resistant triple-negative breast cancer cells with low-dose 6-mercaptopurine and 5-azacitidine.”
DOI - https://doi.org/10.18632/oncotarget.27922
Correspondence to - Anthony Lucci - alucci@mdanderson.org, and Balraj Singh - bsingh@mdanderson.org
Video version - https://www.youtube.com/watch?v=TwIBNkUe1y4
Abstract
Highly adaptable breast cancer cells that can opportunistically switch between proliferation and quiescence are often responsible for disease relapse. We have developed a function-based selection strategy for such resistant cells, exemplified by SUM149-MA and FC-IBC02-MA triple-negative breast cancer cells. We have also reported that a lengthy treatment with low-dose 6-mercaptopurine, a clinically useful anti-inflammatory drug, inhibits such resistant cells. To more rigorously test the clinical suitability of 6-mercaptopurine, here we investigated effects of further lowering its dose and the possibility of overcoming resistance to single-drug treatment by combining the drug with another ribonucleoside analog 5-azacitidine. We found that that a lengthy treatment with 1 μM 5-azacitidine, without a significant effect on cell proliferation, sensitized cancer cells to the inhibitory effects of low-dose 6-mercaptopurine. Importantly, treatment for several weeks with low doses of 6-mercaptopurine and/or 5-azacitidine did not render cancer cells resistant to chemotherapeutic drugs doxorubicin or paclitaxel. In fact, the cells became more sensitive to chemotherapeutic drugs upon treatment with 6-mercaptopurine and/or 5-azacitidine. Our analyses of protein markers of epithelial-to-mesenchymal transition indicated that treatments with 6-mercaptopurine and/or 5-azacitidine do not significantly reverse this process in our model. Our results showed that safe drugs such as low-dose 6-mercaptopurine singly or combined with 5-azacitidine, which are suitable for use prior to disease relapse, have a potential of inhibiting highly resistant triple-negative breast cancer cells.
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27922
Press release - https://www.oncotarget.com/news/pr/inhibition-of-resistant-triple-negative-breast-cancer-cells/
Keywords - resistant TNBC, minimal residual disease, intratumor heterogeneity, breast cancer relapse, metastasis prevention
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new editorial paper was published in Oncotarget on September 8, 2022, by researchers Jingwen Zhu, Joseph N. Miller and John D. Schuetz from St. Jude Children’s Research Hospital in Memphis, Tennessee, entitled, “An ABC transporter as a potential target against SHH-Medulloblastoma: From Benchtop to Bedside.”
Medulloblastoma (MB) is a common malignant pediatric brain tumor divided into four main subgroups (WNT, SHH, Group 3 and 4). The most prevalent MB in children <3 years is the Sonic Hedgehog (SHH) subtype, which arises from granule neuron progenitors with aberrant SHH signaling.
While a standard treatment regimen includes tumor resection followed by a combination of craniospinal irradiation and chemotherapy, recommended treatment for patients <3 years consists of only chemotherapeutics as radiation therapy produces neuro-developmental side-effects. For SHH-MB, smoothened (SMO) inhibitors were initially seen as a promising therapy as SMO is central to SHH pathway activation. However, this approach yielded diminishing returns for young children due to: 1) SMO acquired therapy-induced drug-resistant mutations; 2) treatment with these inhibitors lead to irreversible developmental defects; and 3) gene alterations in SHH signaling downstream from SMO circumvent SMO inhibition. The discovery of novel modulators of the SHH pathway to advance SHH-MB treatment is greatly needed.
“Thus, the identification of novel targetable regulators that function downstream of SMO is desirable to enhance SHH-MB therapy.”
While the involvement of ATP-Binding Cassette (ABC) transporters in drug resistance is well studied, emerging studies have discovered their biological roles in tumorigenesis or cancer progression.
Use of a data-driven systems biology approach led to the identification ABCC4 as a novel target of SHH-MB. Presumably this method could be expanded to uncover ABCC4’s role in other diseases with altered SHH signaling or other cancers in which high expression of ABCC4 is a hallmark of poor prognosis. Therefore, future studies should aim to obtain a better understanding of ABCC4’s biological roles in different cancers and to overcome therapeutic barriers in implementation of ABCC4 inhibitors.
“These aims are fundamental in directing the development of ABCC4 inhibitors towards the ideal therapeutic strategy and providing a helpful guidance for clinical use to attain maximum efficacy.”
DOI: https://doi.org/10.18632/oncotarget.28272
Correspondence to: John D. Schuetz – Email: john.schuetz@stjude.org
Keywords: transporter, chemotherapeutics
About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com.
Dr. Glenn Simmons Jr. from Cornell University College of Veterinary Medicine, and Dr. Stefani Thomas from University of Minnesota School of Medicine, detail a recent review they co-authored that was published by Oncotarget, entitled, “Targeting lipid metabolism in the treatment of ovarian cancer.”
DOI - https://doi.org/10.18632/oncotarget.28241
Correspondence to - Glenn E. Simmons Jr. - glenn.simmons@cornell.edu
Video version - https://www.youtube.com/watch?v=RCvzLXZM1-A
Abstract
Cancer cells undergo alterations in lipid metabolism to support their high energy needs, tumorigenesis and evade an anti-tumor immune response. Alterations in fatty acid production are controlled by multiple enzymes, chiefly Acetyl CoA Carboxylase, ATP-Citrate Lyase, Fatty Acid Synthase, and Stearoyl CoA Desaturase 1. Ovarian cancer (OC) is a common gynecological malignancy with a high rate of aggressive carcinoma progression and drug resistance. The accumulation of unsaturated fatty acids in ovarian cancer supports cell growth, increased cancer cell migration, and worse patient outcomes. Ovarian cancer cells also expand their lipid stores via increased uptake of lipids using fatty acid translocases, fatty acid-binding proteins, and low-density lipoprotein receptors. Furthermore, increased lipogenesis and lipid uptake promote chemotherapy resistance and dampen the adaptive immune response needed to eliminate tumors. In this review, we discuss the role of lipid synthesis and metabolism in driving tumorigenesis and drug resistance in ovarian cancer conferring poor prognosis and outcomes in patients. We also cover some aspects of how lipids fuel ovarian cancer stem cells, and how these metabolic alterations in intracellular lipid content could potentially serve as biomarkers of ovarian cancer.
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28241
Keywords - ovarian cancer, lipid metabolism, biomarkers, microenvironment, fatty acid
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to a press release about a new research paper published by Oncotarget, entitled, “Targeted elastin-like polypeptide fusion protein for near-infrared imaging of human and canine urothelial carcinoma.”
_______________________________
A new research paper was published in Oncotarget on September 6, 2022, entitled, “Targeted elastin-like polypeptide fusion protein for near-infrared imaging of human and canine urothelial carcinoma.”
Bladder cancer (BC) is the 10th most common malignancy, affecting more than half a million people worldwide each year, and accounts for 4.6% of the total new cancer cases in the United States. With urothelial carcinoma (UC), the most common form of BC, the 5-year BC recurrence rate is nearly 78%, necessitating life-long surveillance, making it one of the costliest cancers to treat and manage. Cystoscopic visualization of bladder cancer is an essential method for initial bladder cancer detection and diagnosis, transurethral resection, and monitoring for recurrence.
Researchers Aayush Aayush, Saloni Darji, Deepika Dhawan, Alexander Enstrom, Meaghan M. Broman, Muhammad T. Idrees, Hristos Kaimakliotis, Timothy Ratliff, Deborah Knapp, and David Thompson from Purdue University and Indiana University sought to develop a new intravesical imaging agent that is more specific and sensitive using a polypeptide based NIR (near-infrared) probe designed to detect cells bearing epidermal growth factor receptors (EGFR) that are overexpressed in 80% of urothelial carcinoma (UC) cases. The NIR imaging agent consisted of an elastin like polypeptide (ELP) fused with epidermal growth factor (EGF) and conjugated to Cy5.5 to give Cy5.5-N24-EGF as a NIR contrast agent. In addition to evaluation in human cells and tissues, the agent was tested in canine cell lines and tissue samples with naturally occurring invasive UC.
“Dogs with naturally-occuring UC are an emerging option for a suitable large animal model of BC, where the cancer displays similar microscopic anatomy, histological appearance, biological behavior, heterogeneity, and molecular subtypes and markers to human invasive BC.”
Full press release - https://www.oncotarget.com/news/pr/oncotarget-targeted-elastin-like-polypeptide-fusion-protein-for-near-infrared-imaging-of-human-and-canine-urothelial-carcinoma/
DOI: https://doi.org/10.18632/oncotarget.28271
Correspondence to: David Thompson – davethom@purdue.edu
Keywords: bladder cancer, elastin-like polypeptide, NIR imaging, epidermal growth factor receptor (EGFR), translational studies
About Oncotarget:
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed.
To learn more about Oncotarget, visit Oncotarget.com and connect with us:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com
Listen to a blog summary of a recent research paper published by Oncotarget, entitled, "Immunotherapy Response Predicted by Machine Learning & Gut Microbiomes." __________________________________________
Immunotherapy has become a powerful breakthrough in cancer treatment, however, 50% of patients do not respond to immunotherapy. What internal or external features inhibit or confer patient or tumor response to immune system-harnessing therapeutics? These patient/tumor features that impact responsiveness to immunotherapy have yet to be fully elucidated.
“Increasing evidence has emerged that gut microbial communities help shape the host immune system [9–11].”
Full blog - https://www.oncotarget.org/2022/09/01/immunotherapy-response-predicted-by-machine-learning-gut-microbiomes/
DOI - https://doi.org/10.18632/oncotarget.28252
Correspondence to - Heidi H. Kong - konghe@mail.nih.gov
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632/oncotarget.28252
Keywords - gut microbiome; immunotherapy; 16S rRNA; machine learning; metagenomics
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed.
To learn more about Oncotarget, please visit www.oncotarget.com and connect with us:
SoundCloud - @oncotarget Facebook - www.facebook.com/Oncotarget/ Twitter - twitter.com/oncotarget Instagram - www.instagram.com/oncotargetjrnl/ YouTube - www.youtube.com/OncotargetYouTube LinkedIn - www.linkedin.com/company/oncotarget Pinterest - www.pinterest.com/oncotarget/ Reddit - www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to a blog summary of a recent research paper published by Oncotarget, entitled, "Combined epigenetic and immunotherapy for blastic and classical mantle cell lymphoma." __________________________________________
Mantle cell lymphoma (MCL) is a type of non-Hodgkin’s lymphoma (NHL) that is aggressive, difficult to treat and typically affects older adults. Recurrence and mortality rates among patients with MCL have remained high, despite recent therapeutic advances. Blastic mantle cell lymphoma (bMCL) is a rare subtype of MCL associated with a worse disease trajectory.
“Despite recent advances, MCL is incurable except with allogeneic stem cell transplant. Blastic mantle cell lymphoma (bMCL) is a rarer subtype of cMCL associated with an aggressive clinical course and poor treatment response, frequent relapse and poor outcomes.”
In previous studies, researchers reported that a combination of epigenetic and immunotherapy treatments may have synergistic activity and offer better outcomes in patients with MCL. In the current study, Francis R. LeBlanc, Zainul S. Hasanali, August Stuart, Sara Shimko, Kamal Sharma, Violetta V. Leshchenko, Samir Parekh, Haiqing Fu, Ya Zhang, Melvenia M. Martin, Mark Kester, Todd Fox, Jiangang Liao, Thomas P. Loughran, Juanita Evans, Jeffrey J. Pu, Stephen E. Spurgeon, Mirit I. Aladjem, and Elliot M. Epner from Pennsylvania State University College of Medicine, Penn State Hershey Cancer Institute, Winter Haven Hospital Cassidy Cancer Center, Icahn School of Medicine at Mount Sinai, National Cancer Institute, University of Virginia, UVA Cancer Center, University of Arizona College of Medicine, Oregon Health and Science University, and Beverly Hills Cancer Center used samples from a previous trial to perform correlative studies focused on clinical results in patients with blastic MCL. On August 16, 2022, their research paper was published in Volume 13 of Oncotarget, entitled, “Combined epigenetic and immunotherapy for blastic and classical mantle cell lymphoma.”
Full blog - https://www.oncotarget.org/2022/08/24/epigenetics-and-immunotherapy-combined-fights-rare-lymphoma/
DOI - https://www.oncotarget.com/article/28258/text/
Correspondence to - Francis R. LeBlanc - francis.leblanc@cchmc.org
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28258
Keywords - epigenetics, blastic mantle cell lymphoma, cladribine
About Oncotarget
Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new research paper was published in Oncotarget on August 4, 2022, entitled, “Kinase activity profiling in renal cell carcinoma, benign renal tissue and in response to four different tyrosine kinase inhibitors.”
Kinase activity is frequently altered in renal cell carcinoma (RCC), and tyrosine kinase inhibitors (TKIs) are part of the standard treatment strategy in patients with metastatic disease. However, there are still no established biomarkers to predict clinical benefits of a specific TKI.
“Despite a number of new treatment options improving RCC patients’ disease control rates and survival, the lack of useful biomarkers remains a major clinical concern.”
In the current study, researchers Andliena Tahiri, Katarina Puco, Faris Naji, Vessela N. Kristensen, Glenny Cecilie Alfsen, Lorant Farkas, Frode S. Nilsen, Stig Müller, Jan Oldenburg, and Jürgen Geisler, from University of Oslo, Oslo University Hospital, Akershus University Hospital, and Pamgene International BV, performed protein tyrosine kinase (PTK) profiling using PamChip® technology.
“The aim of this study was to identify differences in PTK activity between normal and malignant kidney tissue obtained from the same patient, and to investigate the inhibitory effects of TKIs frequently used in the clinics: sunitinib, pazopanib, cabozantinib and tivozanib.”
The results showed that 36 kinase substrates differ (FDR < 0.05) between normal and cancer kidney tissue, where members of the Src family kinases and the phosphoinositide-3-kinase (PI3K) pathway exhibit high activity in renal cancer.
Furthermore, ex vivo treatment of clear cell RCC with TKIs revealed that pathways such as Rap1, Ras and PI3K pathways were strongly inhibited, whereas the neurotrophin pathway had increased activity upon TKI addition. Their assay showed that tivozanib and cabozantinib exhibited greater inhibitory effects on PTK activity compared to sunitinib and pazopanib, implying they might be better suitable as TKIs for selected RCC patients.
“The results of our study contribute to better understanding of the changes in kinase activity in RCC tumor cells involved in fundamental oncogenic cellular processes and the ex vivo effect of TKIs. We found tivozanib and cabozantinib to be more potent TKIs in RCC samples than sunitinib or pazopanib. The next step will be to correlate the efficacy and toxicity in individual patients with their respective kinase activity of normal and malignant kidney tissue.”
DOI: https://doi.org/10.18632/oncotarget.28257
Correspondence to: Jürgen Geisler – Email: juergen.geisler@medisin.uio.no
Keywords: kidney cancer, kinase activity, tyrosine kinase inhibitors, renal cell carcinoma, tyrosine kinase
About Oncotarget:
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com.
A new research paper was published in Oncotarget on August 3, 2022, entitled, “Glypican-3 (GPC3) is associated with MCPyV-negative status and impaired outcome in Merkel cell carcinoma.”
Merkel cell carcinoma (MCC) is an aggressive skin cancer, related to the Merkel Cell Polyomavirus (MCPyV) in 80% of cases. Immune checkpoint inhibitors provide sustained benefit in about 50% of MCC patients with advanced disease.
Glypican-3 (GPC3) is an oncofetal tumor antigen that is an attractive target for chimeric antigen receptor T cell therapy due to its highly restricted expression on normal tissue and high prevalence in several solid tumors. GPC3 is known to be expressed in MCC but its association with tumor characteristics or prognosis has not been reported.
In this study, researchers (Sujatha Muralidharan, Thibault Kervarrec, Glen J. Weiss, and Mahtab Samimi) from SOTIO Biotech Inc. and the University Hospital of Tours investigated MCC GPC3 expression by immunohistochemistry (IHC) and its association with tumor characteristics, MCPyV status and patient outcome.
“The aim of the present study was to complete validation of a GPC3 antibody for use in immunohistochemistry (IHC), investigate the expression of GPC3 in MCC by IHC and to assess its association with tumor characteristics, MCPyV status, and patient outcome.”
The GC33 antibody clone was validated for GPC3 IHC staining of tumor specimens in comparison to an established GPC3 IHC antibody. An MCC tissue microarray was stained for GPC3 by IHC using GC33 antibody. Association of GPC3+ IHC with baseline characteristics, MCPyV status (qPCR) and outcome (death from MCC/recurrence) were assessed.
Forty-two of 62 samples (67.7%) were GPC3+. GPC3 expression was more frequently observed in females (p = 0.048) and MCPyV-negative tumors (p = 0.021). By multivariate analysis, GPC3 expression was associated with increased death from disease (CSS) (hazard ratio [HR] 4.05, 95% CI 1.06–15.43), together with advanced age (HR 4.85, 95% CI 1.39–16.9) and male gender (HR 4.64, 95% CI 1.31–16.41).
GPC3 expression is frequent in MCC tumors, especially MCPyV-negative cases, and is associated with increased risk of death. High prevalence of surface GPC3 makes it a putative drug target.
“In this study, we found that GPC3 was expressed in nearly 70% of MCC tumors and up to 90% of MCPyV-negative cases, and was associated with worse prognosis in terms of risk of death from MCC.”
DOI: https://doi.org/10.18632/oncotarget.28260
Correspondence to: Glen J. Weiss - weiss@sotio.com, and Mahtab Samimi - mahtab.samimi@univ-tours.fr
Keywords: Merkel cell carcinoma, glypican-3, Merkel cell polyomavirus, outcome
About Oncotarget:
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com.
A new research paper was published in Oncotarget on August 3, 2022, entitled, “A novel mechanism of regulation of the oncogenic transcription factor GLI3 by toll-like receptor signaling.”
The transcription factor GLI3 is a member of the GLI family and has been shown to be regulated by canonical hedgehog (HH) signaling through smoothened (SMO). Little is known about SMO-independent regulation of GLI3.
“Hedgehog (HH) signaling is well known for its role in embryonic development, cancer and inflammation [1–4]. At the center of HH signaling are the 2 receptors patched (PTCH1) and smoothened (SMO) along with GLI transcription factors [5]. In the absence of HH ligand, PTCH1 inhibits SMO.”
In this study, researchers (Stephan J. Matissek, Mona Karbalivand, Weiguo Han, Ava Boutilier, Estefania Yzar-Garcia, Laura L. Kehoe, Devin Storm Gardner, Adam Hage, Krista Fleck, Vicki Jeffers, Ricardo Rajsbaum, and Sherine F. Elsawa) from the University of New Hampshire and University of Texas Medical Branch identified toll-like receptor (TLR) signaling as a novel pathway regulating GLI3 expression.
The researchers showed that GLI3 expression is induced by LPS/TLR4 in human monocyte cell lines and peripheral blood CD14+ cells. Further analysis identified TRIF, but not MyD88, signaling as the adapter used by TLR4 to regulate GLI3. Using pharmacological and genetic tools, they identified IRF3 as the transcription factor regulating GLI3 downstream of TRIF.
“Furthermore, using additional TLR ligands that signal through TRIF such as the TLR4 ligand, MPLA and the TLR3 ligand, Poly(I:C), we confirm the role of TRIF-IRF3 in the regulation of GLI3.”
They found that IRF3 directly binds to the GLI3 promoter region and this binding was increased upon stimulation of TRIF-IRF3 with Poly(I:C). Using Irf3−/− MEFs, the researchers found that Poly(I:C) stimulation no longer induced GLI3 expression. Finally, using macrophages from mice lacking Gli3 expression in myeloid cells (M-Gli3−/−), they found that in the absence of Gli3, LPS stimulated macrophages secrete less CCL2 and TNF-α compared with macrophages from wild-type (WT) mice.
“Taken together, these results identify a novel TLR-TRIF-IRF3 pathway that regulates the expression of GLI3 that regulates inflammatory cytokines and expands our understanding of the non-canonical signaling pathways involved in the regulation of GLI transcription factors.”
DOI: https://doi.org/10.18632/oncotarget.28261
Correspondence to: Sherine F. Elsawa – Email: sherine.elsawa@unh.edu
Keywords: GLI3, inflammation, TLR
About Oncotarget:
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.
Oncotarget Journal Office 6666 East Quaker Str., Suite 1A Orchard Park, NY 14127 Phone: 1-800-922-0957 (option 2)
Listen to a blog summary of a trending research paper published by Oncotarget on July 28, 2022, entitled, "Diverse geroprotectors differently affect a mechanism linking cellular aging to cellular quiescence in budding yeast." ______________________________________
The mechanisms of cellular aging and cellular quiescence have been preserved throughout evolution. Cellular quiescence is a temporary state of cell cycle arrest and low metabolic activity. Importantly, quiescent (Q) cells maintain the ability to quickly activate and re-enter the cell cycle (in response to the appropriate stimuli). Recent research has shown that cellular quiescence may play a role in cellular aging.
In a 2020 study, research findings indicated that the rate at which yeast cells age is determined by a complicated program that affects 1) when a state of quiescence is entered, 2) how long quiescence is maintained and 3) when the cell exits quiescence. Researchers found that caloric restriction (CR) (a geroprotective intervention) appears to remodel this program, and this remodeling could be responsible for the CR-dependent delay of yeast chronological aging. Thus, the researchers considered the question: Does a single mechanism exist which links cellular aging to cellular quiescence?
“We have introduced a new yeast model for studying mechanisms linking cellular aging to cellular quiescence [109, 110].”
In a new study, researchers (Anna Leonov, Rachel Feldman, Amanda Piano, Anthony Arlia-Ciommo, Jennifer Anne Baratang Junio, Emmanuel Orfanos, Tala Tafakori, Vicky Lutchman, Karamat Mohammad, Sarah Elsaser, Sandra Orfali, Harshvardhan Rajen, and Vladimir I. Titorenko) from Concordia University, Montreal, used a new yeast model to test their hypothesis that a mechanism exists linking cellular aging to cellular quiescence. On July 28, 2022, their research paper was published in Oncotarget and entitled, “Diverse geroprotectors differently affect a mechanism linking cellular aging to cellular quiescence in budding yeast.”
Full blog - https://www.oncotarget.org/2022/08/05/does-a-mechanism-linking-cellular-aging-to-cellular-quiescence-exist/
DOI - https://doi.org/10.18632/oncotarget.28256
Correspondence to - Vladimir I. Titorenko - vladimir.titorenko@concordia.ca
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28256
Keywords - cellular aging, cellular quiescence, longevity, gerotargets, geroprotectors
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new research paper was published in Oncotarget on July 28, 2022, entitled, “Chemoradiation-induced alteration of programmed death-ligand 1, CD8+ tumor-infiltrating lymphocytes and mucin expression in rectal cancer.”
DNA damage and resulting neoantigen formation is considered a mechanism for synergy between radiotherapy and PD-1/PD-L1 pathway inhibition to induce antitumor immune response.
In a new research study, by Marina Baretti, Qingfeng Zhu, Wei Fu, Jeffrey Meyer, Hao Wang, Robert A. Anders, and Nilofer S. Azad from Johns Hopkins University School of Medicine, researchers investigated neoadjuvant chemoradiotherapy (nCRT)-induced changes in CD8+ tumor infiltrating lymphocyte, PD-L1 and mucin expression in rectal cancer patients.
“The synergistic effects of CRT and PD-1/PD-L1 immunotherapy has been supported by several retrospective analyses in different cancer types, including esophageal cancer, bladder cancer, and lung cancer also support[ed] [14, 21, 22]. However, the role of nCRT to interact synergistically with immune checkpoint inhibitor treatment to improve tumor control in rectal cancer remains uncertain.”
Full press release - https://www.oncotarget.com/news/pr/oncotarget-chemoradiation-induced-alteration-of-programmed-death-ligand-cd-tumor-infiltrating-lymphocytes-and-mucin-expression-in-rectal-cancer/
DOI: https://doi.org/10.18632/oncotarget.28255
Correspondence to: Marina Baretti – Email: mbarett1@jh.edu
Keywords: programmed death ligand 1, tumor-infiltrating lymphocytes, immune checkpoints, colorectal cancer, neoadjuvant chemoradiotherapy
About Oncotarget:
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com
A new research paper was published in Oncotarget on July 19, 2022, entitled, “CUDC907, a dual phosphoinositide-3 kinase/histone deacetylase inhibitor, promotes apoptosis of NF2 Schwannoma cells.”
Neurofibromatosis Type 2 (NF2) is a rare tumor disorder caused by pathogenic variants of the merlin tumor suppressor encoded by NF2. Patients develop vestibular schwannomas (VS), peripheral schwannomas, meningiomas, and ependymomas. There are no approved drug therapies for NF2. Previous work identified phosphoinositide-3 kinase (PI3K) as a druggable target.
Researchers Julianne Huegel, Christine T. Dinh, Maria Martinelli, Olena Bracho, Rosa Rosario, Haley Hardin, Michael Estivill, Anthony Griswold, Sakir Gultekin, Xue-Zhong Liu, and Cristina Fernandez-Valle, from the University of Central Florida and the University of Miami Miller School of Medicine, conducted an unbiased chemical compound screen of the Library of Pharmacologically Active Compounds (LOPAC) as a pilot high-throughput screen to identify NF2 schwannoma targets for inhibition.
“Here we screened PI3K pathway inhibitors for efficacy in reducing viability of human schwannoma cells.”
The lead compound, CUDC907, a dual histone deacetylase (HDAC)/PI3K inhibitor, was further evaluated for its effects on isolated and nerve-grafted schwannoma model cells, and primary VS cells. CUDC907 (3 nM IG50) reduced human merlin deficient Schwann cell (MD-SC) viability and was 5–100 fold selective for MD over WT-SCs. CUDC907 (10 nM) promoted cell cycle arrest and caspase-3/7 activation within 24 hours in human MD-SCs. Western blots confirmed a dose-dependent increase in acetylated lysine and decreases in pAKT and YAP.
In a 14-day treatment regimen, CUDC907 decreased tumor growth rate by 44%, modulated phospho-target levels, and decreased YAP levels. In five primary VS, CUDC907 decreased viability, induced caspase-3/7 cleavage, and reduced YAP levels. Its efficacy correlated with basal phospho-HDAC2 levels. CUDC907 has cytotoxic activity in NF2 schwannoma models and primary VS cells and is a candidate for clinical trials.
“In summary, we demonstrated that CUDC907 reduced the activity of three major signaling pathways in NF2 schwannomas (HDAC, PI3K, and YAP) and consistently reduced viability and induced apoptosis in several schwannoma cell models and in all five genetically unique primary VS studied. These consistent results offer the possibility that CUDC907 will promote schwannoma regression in patients with diverse NF2 mutations and support clinical evaluation of CUDC907 for NF2-associated schwannomas and potentially other cancers driven by NF2 pathogenic variants [45]. Current use of this drug in clinical trials for other indications reveals clinical interest in multi-modal drugs over monotherapies.”
DOI: https://doi.org/10.18632/oncotarget.28254
Correspondence to: Cristina Fernandez-Valle – Email: cfv@ucf.edu
Keywords: fimepinostat, Schwann cell, vestibular schwanomma, merlin, nerve allograft
About Oncotarget:
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com.
Listen to the press release about a new research paper published in Volume 13 of Oncotarget, “Predicting cancer immunotherapy response from gut microbiomes using machine learning models.” ___________________________________
A new research paper was published in Oncotarget on July 19, 2022, entitled, “Predicting cancer immunotherapy response from gut microbiomes using machine learning models.”
“In the last decade, the use of cancer immunotherapy targeting immune checkpoint inhibitors (ICIs) to boost T cell mediated cancer cell clearance has significantly improved cancer patient survival [1].”
Cancer immunotherapy has significantly improved patient survival. Yet, half of patients do not respond to immunotherapy. Gut microbiomes have been linked to clinical responsiveness of melanoma patients on immunotherapies; however, different taxa have been associated with response status with implicated taxa inconsistent between studies.
In this new study, by Hai Liang, Jay-Hyun Jo, Zhiwei Zhang, Margaret A. MacGibeny, Jungmin Han, Diana M. Proctor, Monica E. Taylor, You Che, Paul Juneau, Andrea B. Apolo, John A. McCulloch, Diwakar Davar, Hassane M. Zarour, Amiran K. Dzutsev, Isaac Brownell, Giorgio Trinchieri, James L. Gulley, and Heidi H. Kong from the National Institutes of Health Library, National Cancer Institute, National Human Genome Research Institute, West Virginia University, Zimmerman Associates Inc., and the University of Pittsburgh, researchers used a tumor-agnostic approach to find common gut microbiome features of response among immunotherapy patients with different advanced stage cancers.
Full press release - https://www.oncotarget.com/news/pr/oncotarget-predicting-cancer-immunotherapy-response-from-gut-microbiomes-using-machine-learning-models/
DOI - https://doi.org/10.18632/oncotarget.28252
Correspondence to - Heidi H. Kong - konghe@mail.nih.gov
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28252
Keywords - gut microbiome, immunotherapy, 16S rRNA, machine learning, metagenomics
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to a blog summary of a trending research paper published in Volume 13 of Oncotarget, entitled, "Telomere shortening accelerates tumor initiation in the L2-IL1B mouse model of Barrett esophagus and emerges as a possible biomarker." ___________________________________
Smokers are significantly more likely than nonsmokers to have acid reflux. In many Western countries, a popular diet—known for its convenience, availability and, frankly, its lack of nutritional value—is also known to cause acid reflux. Some of the affordable foods and beverages easily accessible to Western consumers include fried food, fast foods, pizza, potato chips (and other processed snacks), high-fat meats (bacon, sausage), cheese, alcohol, soda, energy drinks, and etcetera. Unfortunately, this indulgent type of diet is accompanied by consequences beyond oily skin and an expanding waistband.
BARRETT’S ESOPHAGUS
Chronic acid reflux can lead to gastroesophageal reflux disease. Gastroesophageal reflux disease can lead to Barrett’s esophagus (BE). BE is a premalignant condition in which the lining of the esophagus becomes damaged by acid reflux. BE can lead to the onset of a type of cancer called esophageal adenocarcinoma (EAC). Over the past few decades, statistics have reported that the incidence of EAC in Western populations is increasing.
“Esophageal adenocarcinoma (EAC) is on the rise in western countries with increased incidence and high mortality [1, 2].”
Since the popularity of smoking and a heartburn-inducing diet is likely to continue in the West, the early detection of EAC is critical for improving patient outcomes. If a biomarker could indicate a BE patient’s present risk of EAC, early EAC treatment could curb incidence and mortality rates. However, such a biomarker has yet to be confirmed. On February 14, 2022, researchers from Technische Universität München, Columbia University Irving Medical Center and Universitätsklinikum Freiburg published the research paper, “Telomere shortening accelerates tumor initiation in the L2-IL1B mouse model of Barrett esophagus and emerges as a possible biomarker,” in Oncotarget.
“Here we aimed to provide functional evidence for the hypothesis that telomere shortening can directly contribute to tumor initiation, and thus serve as a potential biomarker for BE cancer risk stratification [22, 24].”
Full blog - https://www.oncotarget.org/2022/07/15/how-heartburn-can-turn-into-esophageal-cancer-and-a-possible-biomarker/
DOI - https://doi.org/10.18632/oncotarget.28198
Correspondence to - Michael Quante - michael.quante@uniklinik-freiburg.de
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28198
Keywords - Barrett's esophagus, telomere shortening, esophageal cancer, risk factor, TERT/TERC
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Dr. Robert Hsu from the Department of Internal Medicine, Division of Medical Oncology, Norris Comprehensive Cancer Center and Hospital, University of Southern California, describes a recent research paper he co-authored that was published by Oncotarget, entitled, “Molecular characterization of Kita-Kyushu lung cancer antigen (KK-LC-1) expressing carcinomas.”
DOI - https://doi.org/10.18632/oncotarget.28132
Correspondence to - Jorge J. Nieva - jorge.nieva@med.usc.edu
Abstract
Cancer/testis antigens (CTAs) are strongly expressed in some solid tumors but minimally expressed in normal tissue, making them appealing therapeutic targets. KK-LC-1 (CXorf61) has cytoplasmic expression in gastric, breast, and lung cancer. We characterized the molecular subtypes of non-small cell lung cancer (NSCLC) expressing KK-LC-1 to inform rational clinical trials of T-cell receptor therapy (TCR-T) targeting KK-LC-1. 9790 NSCLC tumors that underwent whole transcriptome sequencing (Illumina NovaSeq) and NextGen DNA sequencing (NextSeq, 592 Genes and NovaSEQ, WES) at Caris Life Sciences (Phoenix, AZ) were analyzed. Tumors were split into quartiles based on KK-LC-1 expression and pathological and molecular differences were investigated. Adenocarcinoma had significantly higher KK-LC-1 expression than squamous cell carcinoma (median, 3.25 vs. 1.17 transcripts per million (TPM), p < 0.0001). Tumors with the highest quartile of KK-LC-1 expression had a greater proportion of tumors with high tumor mutation burden (TMB) (≥10 mutations per megabase; 44% vs. 28% in Q1, p < 0.001). Increased KK-LC-1 expression was associated with increased M1 macrophage abundance. Higher levels of KK-LC-1 expression were seen in pan-wild type and KRAS mutated tumors and associated with high TMB. TCR-T therapy directed against KK-LC-1 should be considered in patients whose clinical features reflect these characteristics.
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28132
Press release - https://www.oncotarget.com/news/pr/kita-kyushu-lung-cancer-antigen-kk-lc-1-expressing-carcinomas/
Keywords - lung cancer, tumor microenvironment, diagnostic biomarkers, biomarkers for immunotherapy, cancer testis antigen
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A new research paper was published in Oncotarget on June 30, 2022, entitled, “Role of germline variants in the metastasis of breast carcinomas.”
Most cancer-related deaths in breast cancer patients are associated with metastasis, a multistep, intricate process that requires the cooperation of tumor cells, tumor microenvironment and metastasis target tissues. It is accepted that metastasis does not depend on the tumor characteristics but the host’s genetic makeup.
“However, there has been limited success in determining the germline genetic variants that influence metastasis development, mainly because of the limitations of traditional genome-wide association studies to detect the relevant genetic polymorphisms underlying complex phenotypes. “
Full press release: https://www.oncotarget.com/news/pr/oncotarget-role-of-germline-variants-in-the-metastasis-of-breast-carcinomas/
DOI: https://doi.org/10.18632/oncotarget.28250
Correspondence to: Aurelio A. Moya-García - Email: amoyag@uma.es
Special Collection on Breast Cancer: https://www.oncotarget.com/collections/breast-cancer/
Sign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28250
Keywords: breast cancer, germline variants, epistasis, network analysis, seed and soil
About Oncotarget:
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com.
Researchers from Eli Lilly and Company published a new research paper in Oncotarget on July 2, entitled, “Continuous treatment with abemaciclib leads to sustained and efficient inhibition of breast cancer cell proliferation.”
Worldwide, breast cancer (BC) is the second most common cancer. Pharmacologically targeting cyclin-dependent kinase 4 and 6 (CDK4 & 6) has proven to be a successful therapeutic approach in patients with estrogen receptor-positive (ER+) breast cancer.
Abemaciclib is the first FDA-approved CDK4 & 6 inhibitor (CDK4 & 6i) approved for the adjuvant treatment of HR+, HER2–, node-positive, early breast cancer (EBC) at high risk of recurrence and a Ki-67 score ≥20%. Differences have been observed in both efficacy and severity of neutropenia among the available CDK4 & 6i, generating interest in a possible mechanistic explanation. In this study, researchers examined the preclinical attributes of abemaciclib and other CDK4 & 6i using biochemical and cell-based assays.
“In vitro, abemaciclib preferentially inhibited CDK4 kinase activity versus CDK6, resulting in inhibition of cell proliferation in a panel of BC cell lines with higher average potency than palbociclib or ribociclib."
Abemaciclib showed activity regardless of HER2 amplification and phosphatidylinositol 3-kinase (PI3KCA) gene mutation status. In human bone marrow progenitor cells, abemaciclib showed lower impact on myeloid maturation than other CDK4 & 6i when tested at unbound concentrations similar to those observed in clinical trials. Continuous abemaciclib treatment provided profound inhibition of cell proliferation, and triggered senescence and apoptosis.
“After continuous dosing with abemaciclib, cells show sustained inhibition of cell proliferation that leads to irreversible effects through apoptosis. These preclinical results support the differentiated safety and efficacy profile of abemaciclib observed in clinical trials.”
DOI: https://doi.org/10.18632/oncotarget.28249
Correspondence to: María José Lallena - Email: lallena_maria_jose@lilly.com
Special Collection on Breast Cancer: https://www.oncotarget.com/collections/breast-cancer/
Breast Cancer Playlist: https://www.youtube.com/watch?v=za5mOwlmcFM&list=PL1auE_IUnQH5ja5Ukr9S8FWFcbOqR6NHj
Keywords: abemaciclib, breast cancer, cell lines, CDK4/6, continuous dosing
About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OA SoundCloud -https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com
Listen to a blog summary of a research paper published by Genes & Cancer, entitled, "KDM3A/Ets1/MCAM axis promotes growth and metastatic properties in Rhabdomyosarcoma.”
Rhabdomyosarcoma (RMS) and Ewing Sarcoma are among the most common types of cancer that develop in childhood. In recent years, new studies from researchers at the University of Colorado Denver Anschutz Medical Campus have contributed to the expansion of biomedical knowledge about how these diseases progress—paving a way for novel treatment strategies and therapeutics to inhibit the progression of these diseases.
INTRODUCTION RMS consists of two predominant and distinct disease subtypes: fusion-positive RMS (FP-RMS) and fusion-negative RMS (FN-RMS). Fusion-positive RMS is the more aggressive subtype and shows a strong metastatic tendency to spread to other parts of the body. The sarcomagenesis of FP-RMS is driven by a genetic mutation that spawns the abnormal cancer-driving protein PAX3/FOXO1, or P3F. These P3F oncofusion genes use transcriptional and epigenetic mechanisms to drive FP-RMS pathogenesis. However, little was previously known about the mechanisms P3F uses for metastasis.
Recently, a team of dedicated researchers—Lays Martin Sobral, Marybeth Sechler, Janet K. Parrish, Tyler S. McCann, Kenneth L. Jones, Joshua C. Black, and Paul Jedlicka—endeavored to better understand the mechanisms and molecular pathways contributing to RMS progression, including the more aggressive FP-RMS subtype. In 2020, their influential research paper was published in Genes & Cancer and entitled, “KDM3A/Ets1/MCAM axis promotes growth and metastatic properties in Rhabdomyosarcoma.”
Full blog - https://www.impactjournals.com/journals/blog/genesandcancer/how-ewing-sarcoma-led-to-discoveries-in-rhabdomyosarcoma/
Keywords - pediatric cancer, rhabdomyosarcoma, KDM3A, Ets1, metastasis
About Genes & Cancer
Genes & Cancer covers all aspects of the structure and function of oncogenes, growth suppressor and apoptotic genes.
To learn more about Genes & Cancer, please visit https://www.genesandcancer.com/ and connect with us:
Facebook - https://www.facebook.com/GenesandCancer/ Twitter - https://twitter.com/GenesCancerJrnl YouTube - https://www.youtube.com/channel/UCvlxdOvQQymzBWWbxAYyrRw LinkedIn - https://www.linkedin.com/company/genes-&-cancer
Genes & Cancer is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
At the start of 2022, Oncotarget began publishing research papers in a continuous publishing format in yearly volumes. As of June 23, 2022, Oncotarget has published a total of 64 high-impact, oncology-focused papers within Volume 13.
Oncotarget’s Volume 13 consists of papers authored by numerous prestigious researchers and scientists from world-renowned institutions. Select papers in this Volume were chosen for inclusion in Oncotarget’s Special Collections on breast and lung cancer research.
Read the full press release - https://www.oncotarget.net/2022/06/23/oncotarget-new-oncology-focused-papers-published-in-volume-13/
Visit www.Oncotarget.com to read the latest publications in Volume 13.
About Oncotarget:
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com.
BUFFALO, NY- June 16, 2022 – Oncology-focused research papers published in Volume 12 of Genes & Cancer are now on PubMed.
Read short previews about some of the groundbreaking studies published in 2021 by Genes & Cancer. Visit YouTube to watch video previews of studies published by Genes & Cancer.
Full press release - https://www.impactjournals.com/journals/blog/genesandcancer/genes-cancer-now-on-pubmed-volume-12/
About Genes & Cancer:
Genes & Cancer covers all aspects of the structure and function of oncogenes, growth suppressor and apoptotic genes, their role in signal transduction and the mechanisms by which their expression and function are altered during tumor development. In addition to publishing manuscripts that directly relate to these areas of research, Genes & Cancer also aims to attract papers in the areas of genomics, drug development and systems biology.
To learn more about Genes & Cancer, visit www.genesandcancer.com and connect with us on social media:
Twitter - https://twitter.com/GenesCancerJrnl Facebook - https://www.facebook.com/GenesandCancer YouTube - https://www.youtube.com/channel/UCvlxdOvQQymzBWWbxAYyrRw/featured LinkedIn - https://www.linkedin.com/company/genes-&-cancer/
For media inquiries, please contact: media@impactjournals.com.
Genes & Cancer Journal Office 6666 East Quaker Str., Suite 1C Orchard Park, NY 14127 Phone: 1-212-659-5400
The Ride for Roswell is one of the nation’s largest cycling events—hosted by Roswell Park Comprehensive Cancer Center—to raise awareness and funds for cancer research and patient care. This charity bike ride, based out of Buffalo, New York, has brought people together for 26 years to celebrate cancer survivors, pay tribute to lives that have been lost, and to work together to support research and find a cure.
When it opened its doors in Buffalo in 1898, Roswell Park Comprehensive Cancer Center was the first cancer research-focused institution in the world. Today, this institution is one of only four National Cancer Institute-designated comprehensive cancer centers in the state of New York. Roswell Park Comprehensive Cancer Center is ranked by U.S. News & World Report as one of the best cancer hospitals in the United States.
Full press release - https://www.impactjournals.com/journals/blog/news/impact-journals-sponsors-2022-ride-for-roswell/
Visit the Open Access team page to join or donate today - https://give.roswellpark.org/site/TR/SpecialEvents/General?fr_id=1750&pg=team&team_id=8502
More about Impact Journals:
Impact Journals is an open-access publisher, focusing on topics surrounding cancer research, all fields of aging research, and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Our goal is life without disease.
To learn more about Impact Journals, or any of our journals, please visit www.impactjournals.com.
Follow Impact Journals on social media:
Twitter – https://twitter.com/ImpactJrnls Facebook – https://www.facebook.com/ImpactJrnls Oncotarget YouTube Channel – www.youtube.com/c/OncotargetYouTube Aging YouTube Channel – www.youtube.com/c/Aging-US LinkedIn – www.linkedin.com/company/impact-journals/
For media requests, please contact media@impactjournals.com.
Dr. Alexander Pohlman from Rush Medical College, Rush University Medical Center, Chicago, IL, describes a recent review published by Oncotarget that he co-authored entitled, “The role of IGF-pathway biomarkers in determining risks, screening, and prognosis in lung cancer.”
DOI - https://doi.org/10.18632/oncotarget.28202
Correspondence to - Jeffrey A. Borgia - jeffrey_a_borgia@rush.edu
Abstract
Background: Detection rates of early-stage lung cancer are traditionally low, which contributes to inconsistent treatment responses and high rates of annual cancer deaths. Currently, low-dose computed tomography (LDCT) screening produces a high false discovery rate. This limitation has prompted research to identify biomarkers to more clearly define eligible patients for LDCT screening, differentiate indeterminate pulmonary nodules, and select individualized cancer therapy. Biomarkers within the Insulin-like Growth Factor (IGF) family have come to the forefront of this research.
Main Body: Multiple biomarkers within the IGF family have been investigated, most notably IGF-I and IGF binding protein 3. However, newer studies seek to expand this search to other molecules within the IGF axis. Certain studies have demonstrated these biomarkers are useful when used in combination with lung cancer screening, but other findings were not as conclusive, possibly owing to measurement bias and non-standardized assay techniques. Research also has suggested IGF biomarkers may be beneficial in the prognostication and subsequent treatment via systemic therapy. Despite these advances, additional knowledge of complex regulatory mechanisms inherent to this system are necessary to more fully harness the potential clinical utility for diagnostic and therapeutic purposes.
Conclusions: The IGF system likely plays a role in multiple phases of lung cancer; however, there is a surplus of conflicting data, especially prior to development of the disease and during early stages of detection. IGF biomarkers may be valuable in the screening, prognosis, and treatment of lung cancer, though their exact application requires further study.
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28202
Keywords - IGF, lung cancer, biomarkers, screening, prognostication
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
BUFFALO, NY- June 8, 2022 – A research paper was recently published in Oncotarget, entitled, “A novel group of genes that cause endocrine resistance in breast cancer identified by dynamic gene expression analysis.”
Breast cancer (BC) is the most common type of cancer diagnosed in women. Among female cancer deaths, BC is the second leading cause of death worldwide.
For estrogen receptor-positive (ER-positive) breast cancers, endocrine therapy is an effective therapeutic approach. However, in many cases, ER-positive tumors become unresponsive to endocrine therapy, and tumor regrowth can occur after treatment. While some genetic mutations contribute to resistance in some patients, the underlying causes of resistance to endocrine therapy are mostly undetermined.
“Endocrine therapies have been successful at improving cancer outcomes; however, the development of endocrine resistance, or resistance to inhibition of ER actions, remains a roadblock in breast cancer treatment.”
In the current study, researchers from UTHealth Houston, University of Chicago, University of Texas MD Anderson Cancer Center, and the University of Houston explored the dynamic behavior of the entire gene population to identify novel genes that play fundamental roles in the development and progression of endocrine-resistant breast cancer.
“In this study, we utilized a recently developed statistical approach to investigate the dynamic behavior of gene expression during the development of endocrine resistance and identified a novel group of genes whose time course expression significantly change during cell modelling of endocrine resistant BC development.”
To better understand the process of acquiring endocrine resistance and its underlying gene expression patterns, the researchers applied their recently developed statistical pipeline to datasets from a public functional genomics repository. They found dynamically regulated genes active in the process of endocrine resistance development and progression.
Their dynamic gene expression analysis identified 34 novel genes that significantly changed during cell modeling of endocrine-resistant breast cancer development. Expression of a subset of these genes was also differentially expressed in microarray analysis of endocrine-resistant and endocrine-sensitive tumor samples. Surprisingly, a subset of those genes was also differentially expressed in triple-negative breast cancer (TNBC) as compared with ER-positive BC.
“The findings suggest shared genetic mechanisms may underlie the development of endocrine resistant BC and TNBC.”
DOI: https://doi.org/10.18632/oncotarget.28225
Correspondence to: Michihisa Umetani – mumetani@uh.edu, and Vahed Maroufy – Vahed.Maroufy@uth.tmc.edu
Special Collection on Breast Cancer: https://www.oncotarget.com/collections/breast-cancer/
Keywords: breast cancer, triple negative breast cancer, gene expression profiling, endocrine resistance, gene clustering
About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com.
Listen to a blog summary of a trending research paper published in Volume 13, entitled, “NF-κB over-activation portends improved outcomes in HPV-associated head and neck cancer.” ______________________________
Over the last 10 years in the United States, the human papillomavirus (HPV) has caused more head and neck squamous cell carcinomas (HNSCC) than uterine cervical cancers. Primarily caused either by exposure to HPV or to ethanol or tobacco, HNSCC is a disease that impairs fundamental tissues involved in respiration, speech and digestion. HPV-positive and -negative HNSCC have contrasting clinical, epidemiological and histological features.
“A major discovery in the recent past is that HPV associated HNSCC have improved survival compared to tobacco associated tumors.”
Therefore, treating HNSCC in accordance with HPV status is crucial for avoiding unnecessarily harsh therapeutic side effects in HPV+ HNSCC patients. However, while oncologic outcomes among patients with HPV+ HNSCC are generally favorable, approximately 30% experience a more aggressive disease course and recurrence. Coupled with increasing incidence worldwide, this highlights a growing need for the development of effective clinical stratification tools to accurately identify HPV+ HNSCC patients who have a good or poor prognosis.
In a new study, researchers—from Columbia University, University of Illinois Cancer Center, University of North Carolina at Chapel Hill, and Yale School of Medicine—developed a new tool aimed at better classifying HPV+ HNSCC patients with good or poor prognosis in an effort to personalize treatment and improve patient outcomes. Their trending research paper was published in Oncotarget on May 24, 2022, and entitled, “NF-κB over-activation portends improved outcomes in HPV-associated head and neck cancer.”
“To improve on genomic classification, we designed this study to provide a foundation for development of NF-κB related, RNA based classification strategies to better identify HPV+ HNSCC patients with good or poor prognosis that could potentially aid in future efforts towards treatment personalization.”
Full blog - https://www.oncotarget.org/2022/05/26/new-tool-uses-nf-%ce%bab-activity-to-classify-hpv-head-and-neck-cancer/
DOI - https://doi.org/10.18632/oncotarget.28232
Correspondence to - Wendell G. Yarbrough - dell@med.unc.edu, and Natalia Issaeva - natalia.isaeva@med.unc.edu
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28232
Press release - https://www.oncotarget.com/news/pr/oncotarget-nf-b-over-activation-portends-improved-outcomes-in-hpv-associated-head-and-neck-cancer/
Keywords - HPV, head and neck cancer, CYLD, TRAF3, NF-κB
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
BUFFALO, NY- May 25, 2022 – A new research paper was published in Oncotarget, entitled, “NF-κB over-activation portends improved outcomes in HPV-associated head and neck cancer.”
Head and neck squamous cell carcinoma (HNSCC) is a devastating disease that impairs fundamental tissues involved in respiration, phonation and digestion. HNSCC is primarily caused by exposure to either ethanol and tobacco or the human papillomavirus (HPV). Among patients with HPV+ HNSCC, there is a growing clinical demand to develop robust stratification tools to accurately identify patients with good or poor prognosis.
“While oncologic outcomes for HPV+ HNSCC are generally favorable, treatment paradigms developed for HPV-negative disease burden many survivors of HPV+ HNSCC with lifelong debilitating treatment-associated side effects [10]. On the other hand, ~30% of HPV+ HNSCC patients exhibit a more aggressive disease course and suffer recurrence [11, 12].”
Somatic mutations or deletions in TRAF3 or CYLD identified a subset of HPV+ HNSCC associated with improved outcome. A cross talk between canonical and non-canonical NF-κB signaling suggests that TRAF3 and CYLD affect both NF-κB pathways.
“Herein, we demonstrate that an RNA-based classifier trained on tumors harboring these mutations may improve prognostic classification (Figure 3A, 3B, Figure 4B and Supplementary Figure 1).”
To improve on genomic classification, researchers designed the current study to provide a foundation for development of NF-κB related, RNA based classification strategies to better identify HPV+ HNSCC patients with good or poor prognosis that could potentially aid in future efforts towards treatment personalization.
“This report validates and expands on our findings that significant expression changes related to NF-κB activity occur in the subset of HPV+ HNSCC tumors marked by TRAF3 or CYLD mutations. We are planning future studies investigating the importance of ‘long-tail’ mutations in the NF-κB pathway which might further illuminate the origins of NF-κB dysregulation in HPV+ HNSCC.”
“Given that methods to identify patients for deintensified therapy are imperfect, our improved classifiers may serve as prognostic biomarker to help clinicians with therapeutic decisions.”
DOI: https://doi.org/10.18632/oncotarget.28232
Correspondence to: Wendell G. Yarbrough and Natalia Issaeva
Email: dell@med.unc.edu and natalia.isaeva@med.unc.edu
Keywords: HPV, head and neck cancer, CYLD, TRAF3, NF-κB
About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget
For media inquiries, please contact: media@impactjournals.com.
BUFFALO, NY- May 19, 2022 – A new research paper was published in Volume 13 of Oncotarget, entitled, “CancerOmicsNet: a multi-omics network-based approach to anti-cancer drug profiling.”
Researchers from Louisiana State University developed CancerOmicsNet—a graph neural network model to predict the growth rate of a cancer cell line after drug treatment.
“CancerOmicsNet is more advanced than many deep learning techniques operating in the Euclidean space [47], because it extracts knowledge directly from biological networks providing a more adequate representation of complex diseases such as cancer.”
CancerOmicsNet integrates multiple heterogeneous data, such as biological networks, genomics, inhibitor profiling, and gene-disease associations, into a unified graph structure. This novel method utilizes compact, cancer-specific networks constructed from protein-protein interactions, differential gene expression, disease-gene association, and drug inhibition data.
“In order to evaluate the performance of CancerOmicsNet, we conducted a cross-validation at the tissue level by removing from model training all cell lines originating from a particular tissue and then analyzing the accuracy for these cell lines.”
In this study, the researchers carefully evaluated the generalizability of CancerOmicsNet in a series of cross-validation benchmarks against different tumor tissues. Encouragingly, the cross-validated accuracy of CancerOmicsNet at the tissue level was significantly higher than those measured for other approaches on the same data.
“The performance of CancerOmicsNet, properly cross-validated at the tissue level, is 0.83 in terms of the area under the receiver operating characteristics, which is notably higher than those measured for other approaches.”
The researchers specify that the applicability of CancerOmicsNet is presently limited to kinase inhibitors, while alternative methods are applicable to other classes of therapeutics as well.
“Overall, CancerOmicsNet offers a high performance and the desired generalizability in the prediction of the effect of kinase-targeted therapies on the cancer cell growth.”
DOI: https://doi.org/10.18632/oncotarget.28234
Correspondence to: Michal Brylinski – Email: michal@brylinski.org
Keywords: cancer growth rate, kinase inhibitors, differential gene expression, gene-disease association, cancer-specific networks
About Oncotarget
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.
Listen to a blog summary of a trending research paper published by Oncotarget, entitled, "Proteomic analysis reveals dual requirement for Grb2 and PLCγ1 interactions for BCR-FGFR1-Driven 8p11 cell proliferation." ___________________________________________
Chromosomes are found in the nucleus of cells and consist of proteins and tightly coiled strands of DNA. During cell division, chromosomal translocations can occur while the chromosomes are being copied. This type of mutation can mean that an entire chromosome has moved to another location, or that a chromosome has broken, usually into two pieces, and moved to another site. Some translocations are harmless, but others can lead to aberrant cell proliferation and cancer.
“Over the last half century, chromosomal translocations encoding functional oncogenic proteins have been identified as drivers of multiple cancers, and account for 20% of all malignant neoplasms [1, 2].”
For example, the t(8;22)(p11;q11) chromosomal translocation leads to the initiation of an oncogenic fusion protein called the Breakpoint Cluster Region Fibroblast Growth Factor Receptor 1 (BCR-FGFR1). BCR-FGFR1 is a single driver of 8p11 myeloproliferative syndrome, which is also known as stem cell leukemia/lymphoma (SCLL).
“Stem cell leukemia/lymphoma (SCLL) exhibits distinct clinical and pathological features characterized by chromosomal translocations involving the FGFR1 gene at chromosome 8p11.”
In a trending new study, researchers from the University of California San Diego and Sanford Burnham Prebys Medical Discovery Institute examined mutations in PLCγ1 and Grb2 binding sites individually and when combined together in a double mutant within BCR-FGFR1. On May 11, 2022, the research paper was published in Oncotarget and entitled, “Proteomic analysis reveals dual requirement for Grb2 and PLCγ1 interactions for BCR-FGFR1-Driven 8p11 cell proliferation.”
Full blog - https://www.oncotarget.org/2022/05/12/trending-with-impact-dual-requirement-in-stem-cell-leukemia-lymphoma/
DOI - https://doi.org/10.18632/oncotarget.28228
Correspondence to - Daniel J. Donoghue - ddonoghue@ucsd.edu
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28228
Keywords - oncogenic fusion protein, chromosomal translocation, protein interactome, phosphoproteome, stem cell leukemia/lymphoma
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
BUFFALO, NY-May 16, 2022 – Impact Journals (based out of Buffalo, New York) is an international open-access publisher of journals in the field of biomedical sciences. Impact Journals is on a mission to provide scientists with the opportunity to share exceptional discoveries, offer services that enable rapid dissemination of results, and present vital findings from the many fields of biomedical science. This mission cannot be accomplished without following strong ethical standards.
Scientific integrity is a crucial component of scholarly publishing. At Impact Journals, a growing industry of digital technologies, tools, and ideas are constantly being added to a robust scientific integrity process. The Impact Journals Scientific Integrity Process is built around six main components:
1-Presence of ethics statements 2-Adherence to Industry Standards for Scientific Publishing 3-Rigorous and Insightful Peer Review 4-Elimination of Plagiarism 5-Image Forensics Service 6-If a problem arises post-publication, Impact Journals conducts investigations following COPE guidelines in cooperation with the authors and their affiliated institution.
During the 12:00pm Industry Breakout Session on June 1, Impact Journals will be presenting its full scientific integrity process at the 2022 Society for Scholarly Publishing (SSP) Annual Meeting at the Sheraton Grand Chicago Riverwalk in Chicago, Illinois.
More about Impact Journals:
Impact Journals is an open-access publisher, focusing on topics surrounding cancer research, all fields of aging research, and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Our goal is life without disease.
To learn more about Impact Journals, or any of our journals, please visit www.impactjournals.com.
Follow Impact Journals on social media:
Twitter – https://twitter.com/ImpactJrnls Facebook – https://www.facebook.com/ImpactJrnls Oncotarget YouTube Channel – www.youtube.com/c/OncotargetYouTube LinkedIn – www.linkedin.com/company/impact-journals/
For media requests, please contact media@impactjournals.com.
Dr. Mark Woodford, Assistant Professor at the Department of Urology, SUNY Upstate Medical University, Syracuse, NY, describes his experience publishing the meeting report, “Seventh BHD international symposium: recent scientific and clinical advancement,” with Oncotarget.
DOI - https://doi.org/10.18632/oncotarget.28176
Correspondence to - Mehdi Mollapour - mollapom@upstate.edu
Abstract
The 7th Birt-Hogg-Dubé (BHD) International Symposium convened virtually in October 2021. The meeting attracted more than 200 participants internationally and highlighted recent findings in a variety of areas, including genetic insight and molecular understanding of BHD syndrome, structure and function of the tumor suppressor Folliculin (FLCN), therapeutic and clinical advances as well as patients’ experiences living with this malady.
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28176
Keywords - Birt-Hogg-Dubé syndrome, folliculin, FLCN, tuberous sclerosis complex, LDHA
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to a blog summary of a research paper published by Oncotarget in Volume 13, entitled, "Bladder cancer survival in patients with NOD2 or CDKN2A variants.”
_______________________________
Genitourinary cancers are a group of cancers that affect components of the urinary tract, including the bladder and kidneys. Worldwide, bladder and kidney cancer impact men at disproportionately higher rates than women. While incidence and mortality rates of bladder cancer in most western European countries have been consistently decreasing, some countries in the region, such as Poland, have seen an increase. Bladder cancer is the 4th most common malignancy in Polish men and the 14th most common malignancy in Polish women. There is currently a need to identify more effective bladder cancer biomarkers and therapeutic targets to develop new effective treatments that improve patient outcomes.
“The association between the NOD2 c.3020insC allele and CDKN2A missense variant c.442G>A (p.P.A148T) and survival of patients with bladder or kidney cancer remains controversial.”
In April of 2022, researchers from Pomeranian Medical University, University of Newcastle and NSW Health Pathology published the first larger-scale study in Poland to describe the clinical characteristics and survival of bladder cancer patients and kidney cancer patients associated with variants in NOD2 and CDKN2A. Their research paper was published in Oncotarget on April 22, 2022, and entitled, “Bladder cancer survival in patients with NOD2 or CDKN2A variants.”
Full blog - https://www.impactjournals.com/journals/blog/oncotarget/gene-variants-investigated-in-polish-bladder-and-kidney-cancer/
DOI - https://doi.org/10.18632/oncotarget.28226
Correspondence to - Elżbieta Złowocka-Perłowska - elzunik@wp.pl
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28226
Keywords - bladder cancer, kidney cancer, NOD2, CDKN2A, survival
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to a blog summary of a trending research paper published by Oncotarget in Volume 13, entitled, "Real-world survival analysis by tumor mutational burden in non-small cell lung cancer: a multisite U.S. study." ___________________________________
While a high tumor mutational burden (TMB) may seem unfavorable in the midst of battling non-small cell lung cancer (NSCLC), a higher TMB has been associated with a higher number of neoantigens. The presence of more neoantigens can potentially elicit a stronger immune response. Therefore, TMB may be a viable biomarker of tumor response to immunotherapeutic agents. However, the definitions, parameters and units used to measure high- and low-TMB have been inconsistent over the years. Today, the consensus unit for reporting TMB has shifted to mutations per megabase (mut/Mb). The common cut-off for high- vs. low-TMB from tissue samples is >10 mut/Mb in NSCLC.
“Despite inconsistencies with TMB definition and reporting over time, high TMB has consistently been associated with improved clinical benefit among patients receiving immunotherapy for NSCLC [22].”
Researchers—from University of Utah, University of Minnesota Duluth, Huntsman Cancer Institute, H. Lee Moffitt Cancer Center and Research Institute, Baptist Health Medical Group, MetroHealth Medical Center, Rutgers Cancer Institute of New Jersey, University of Southern California, Saint Luke’s Cancer Institute, University of Kentucky, and Bristol Myers Squibb—used the newest consensus unit and common cut-off parameters for TMB expression to measure TMB’s relationship to treatment response and survival outcomes among metastatic NSCLC patients. Their trending research paper was published in Oncotarget’s Volume 13 on January 31, 2022, and entitled, “Real-world survival analysis by tumor mutational burden in non-small cell lung cancer: a multisite U.S. study.”
“The purpose of this study is to evaluate clinical outcomes by TMB among NSCLC patients treated with immunotherapy containing regimens in the first-line setting.”
Full blog - https://www.oncotarget.org/2022/04/21/trending-with-impact-analysis-of-mutational-burden-in-nsclc/
DOI - https://doi.org/10.18632/oncotarget.28178
Correspondence to - Connor Willis - Connor.Willis@pharm.utah.edu
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28178
Press release - https://www.oncotarget.com/news/pr/oncotarget-mutational-burden-in-lung-cancer-studied-in-multisite-cohort/
Keywords - lung neoplasma, tumor biomarkers, immunotherapy
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
BUFFALO, NY-April 25, 2022 – A new research paper, entitled, “Real-world survival analysis by tumor mutational burden in non-small cell lung cancer: a multisite U.S. study,” was published in Oncotarget on January 31, 2022, by researchers from University of Utah, University of Minnesota Duluth, Huntsman Cancer Institute, H. Lee Moffitt Cancer Center and Research Institute, Baptist Health Medical Group, MetroHealth Medical Center, Rutgers Cancer Institute of New Jersey, University of Southern California, Saint Luke’s Cancer Institute, University of Kentucky, and Bristol Myers Squibb.
This multidisciplinary research team analyzed tumor mutational burden (TMB) among a large cohort of patients who had been diagnosed with stage IV non-small cell lung cancer (NSCLC). The cohort included 667 patients recruited from nine different academic and community cancer centers across the United States.
“The purpose of this study is to evaluate clinical outcomes by TMB among NSCLC patients treated with immunotherapy containing regimens in the first-line setting.” (Source, 2022)
While having a high TMB may sound unfavorable, a higher TMB has been associated with a higher number of neoantigens. The presence of a greater number of neoantigens may potentiate a stronger immune response. Thus, TMB may be a viable biomarker of tumor response to immuno-oncology agents.
“Based on the results in this study and prior research, TMB along with other biomarkers, such as PD-L1, may help identify patients more likely to benefit from first-line immunotherapy.” (Source, 2022)
Results of the study confirmed the association between a higher TMB and smoking history. However, the study did not show an association between TMB and sex, age or tumor histology. The team found that, among patients treated with first-line immunotherapy, TMB levels greater than or equal to 10 mutations per megabase were significantly associated with improved overall survival and progression-free survival.
DOI: https://doi.org/10.18632/oncotarget.28178
Corresponding author: Connor Willis – Connor.Willis@pharm.utah.edu
Video: https://youtu.be/Q5JI4L6Moq0
Sign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28178
About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget
For media inquiries, please contact media@impactjournals.com.
Dr. Stanley Lipkowitz and Dr. Yoshimi Endo Greer from the Women’s Malignancies Branch at the National Cancer Institute discuss a research paper they co-authored that was published by Oncotarget in 2018, entitled, "ONC201 kills breast cancer cells in vitro by targeting mitochondria."
DOI - https://doi.org/10.18632/oncotarget.24862
Correspondence to - lipkowis@mail.nih.gov
Abstract
We report a novel mechanism of action of ONC201 as a mitochondria-targeting drug in cancer cells. ONC201 was originally identified as a small molecule that induces transcription of TNF-related apoptosis-inducing ligand (TRAIL) and subsequently kills cancer cells by activating TRAIL death receptors. In this study, we examined ONC201 toxicity on multiple human breast and endometrial cancer cell lines. ONC201 attenuated cell viability in all cancer cell lines tested. Unexpectedly, ONC201 toxicity was not dependent on either TRAIL receptors nor caspases. Time-lapse live cell imaging revealed that ONC201 induces cell membrane ballooning followed by rupture, distinct from the morphology of cells undergoing apoptosis. Further investigation found that ONC201 induces phosphorylation of AMP-dependent kinase and ATP loss. Cytotoxicity and ATP depletion were significantly enhanced in the absence of glucose, suggesting that ONC201 targets mitochondrial respiration. Further analysis indicated that ONC201 indirectly inhibits mitochondrial respiration. Confocal and electron microscopic analysis demonstrated that ONC201 triggers mitochondrial structural damage and functional impairment. Moreover, ONC201 decreased mitochondrial DNA (mtDNA). RNAseq analysis revealed that ONC201 suppresses expression of multiple mtDNA-encoded genes and nuclear-encoded mitochondrial genes involved in oxidative phosphorylation and other mitochondrial functions. Importantly, fumarate hydratase deficient cancer cells and multiple cancer cell lines with reduced amounts of mtDNA were resistant to ONC201. These results indicate that cells not dependent on mitochondrial respiration are ONC201-resistant. Our data demonstrate that ONC201 kills cancer cells by disrupting mitochondrial function and further suggests that cancer cells that are dependent on glycolysis will be resistant to ONC201.
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.24862
Press release - https://www.oncotarget.com/index.php?journal=oncotarget&page=news&op=press&item=onc201-kills-breast-cancer-cells-in-vitro-by-targeting-mitochondria
Keywords - ONC201, breast cancer, mitochondria
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to a blog summary of a recent research paper published in Volume 13, entitled, "A novel group of genes that cause endocrine resistance in breast cancer identified by dynamic gene expression analysis." _________________________________
Hormones can cause tumor growth in some subtypes of breast cancer. Endocrine therapy, also known as hormone therapy, is a type of cancer treatment that removes or blocks the hormones which fuel breast cancer growth. This treatment is often given as adjuvant therapy after breast cancer surgery to lower the risk of cancer reoccurrence. In some cases, endocrine therapy may be used as a first-line treatment for hormone receptor-positive breast cancers, such as estrogen receptor-positive (ER-positive) breast cancers. However, ER-positive tumors frequently become unresponsive to endocrine therapy, and tumor regrowth can occur after treatment. The underlying causes of endocrine resistance are mostly undetermined.
“Endocrine therapies have been successful at improving cancer outcomes; however, the development of endocrine resistance, or resistance to inhibition of ER actions, remains a roadblock in breast cancer treatment.”
Recently, researchers—from UTHealth Houston, University of Chicago, University of Texas MD Anderson Cancer Center, and the University of Houston—used a new statistical and computational pipeline method of analysis to study the dynamic behavior of gene expression during the development of endocrine resistance in breast cancer. Their trending research paper published in Oncotarget on April 06, 2022, is entitled, “A novel group of genes that cause endocrine resistance in breast cancer identified by dynamic gene expression analysis.”
Full blog - https://www.oncotarget.org/2022/04/14/trending-with-impact-genes-identified-in-endocrine-therapy-resistance/
DOI - https://doi.org/10.18632/oncotarget.28225
Correspondence to - Michihisa Umetani - mumetani@uh.edu, and Vahed Maroufy - Vahed.Maroufy@uth.tmc.edu
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28225
Keywords - breast cancer, triple negative breast cancer, gene expression profiling, endocrine resistance, gene clustering
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Jonathan Kelber and Francesca Sanchez from the Department of Biology, California State University Northridge, Northridge CA, discuss a research paper they co-authored for Oncotarget in 2019, entitled, "Secretomes from metastatic breast cancer cells, enriched for a prognostically unfavorable LCN2 axis, induce anti-inflammatory MSC actions and a tumor-supportive premetastatic lung."
DOI - https://doi.org/10.18632/oncotarget.26903
Correspondence to - jonathan.kelber@csun.edu
Abstract
Cancer metastasis is responsible for the clear majority of cancer-related deaths. Survival and expansion of cancer cells at secondary sites requires that these premetastatic microenvironments be primed by primary tumor cells and their secreted factors. Efforts to date have been limited by immune-deficient in vivo models and/or the need for finely-tuned analysis time points that reduce contributions from early-disseminating cancer cells. In this regard, we developed a tumor cell-free syngeneic breast cancer model for characterizing tumor cell secretome-mediated reprogramming of premetastatic tissues. We demonstrate that secretomes from metastatic breast cancer cells differentially regulate the lung and brain, promoting a tumor-supportive lung microenvironment with both elevated CD73 expression and decreased TNFα expression. Using in vitro models of CD73-positive mesenchymal stem cells (MSCs) and macrophages/monocytes, we tested whether MSCs can mediate anti-inflammatory effects of metastatic breast cancer cells. Notably, conditioned media from metastatic Py230 cells reprogrammed the secretomes of MSCs toward an anti-inflammatory state. Mining transcriptome data from Py8119 and Py230 cells revealed a lipocalin 2 (LCN2) axis that is selectively expressed in the metastatic Py230 cells, predicts poor breast cancer patient survival and is elevated in circulating serum of mice chronically treated with conditioned media from Py230 cells. Taken together, these results establish the utility of an immune-competent tumor cell-free model for characterizing the mechanisms of breast cancer cell priming of the premetastatic niche, demonstrate that MSCs can mediate the anti-inflammatory effects of metastatic breast cancer cells and substantiate LCN2 as a promising therapeutic target for blocking breast cancer progression.
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.26903
Press release - https://www.oncotarget.com/index.php?journal=oncotarget&page=news&op=press&item=secretomes-from-metastatic-breast-cancer-cells-enriched-for-a-prognostically-unfavorable-lcn2-axis-induce-anti-inflammatory-msc-actions-and-a-tumor-supportive-premetastatic-lung
WATCH breast cancer playlist on Youtube - https://www.youtube.com/watch?v=za5mOwlmcFM&list=PL1auE_IUnQH5ja5Ukr9S8FWFcbOqR6NHj
Keywords - premetastatic niche, tumor microenvironment, metastasis, breast cancer secretomes, LCN2
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to a blog summary of a trending research paper published by Oncotarget in Volume 13, entitled, "Role of the prorenin receptor in endometrial cancer cell growth."
_________________________________
In the United States and worldwide, the incidence and mortality rates of endometrial cancer among women have been increasing in recent years. While endometrial cancer is highly treatable, the primary treatment is a surgical hysterectomy. Hysterectomies can have serious side effects and painful personal consequences.
The rise of this gynecological cancer has driven researchers to investigate viable targets and biomarkers for use in endometrial cancer diagnosis, prognosis prediction and alternative therapeutic strategies. In a new study, researchers—from the University of Newcastle, University of Technology Sydney, Monash University, and the University of Melbourne—investigated the (pro)renin receptor ((P)RR) and its role and interactions in the biology of endometrial cancer. Their trending research paper, published in Oncotarget on April 1, 2022, was entitled, “Role of the prorenin receptor in endometrial cancer cell growth.”
Full blog - https://www.oncotarget.org/2022/04/06/novel-therapeutic-strategies-against-endometrial-cancer/
DOI - https://doi.org/10.18632/oncotarget.28224
Correspondence to - Kirsty G. Pringle - kirsty.pringle@newcastle.edu.au
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28224
Keywords - (P)RR; ATP6AP2, endometrial cancer, cellular viability, cellular proliferation
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Mariana Perepitchka, Yekaterina Galat, and Dr. Vasiliy Galat discuss their 2020 research paper published by Oncotarget, entitled, "Down syndrome iPSC model: endothelial perspective on tumor development."
DOI - https://doi.org/10.18632/oncotarget.27712
Correspondence to - Mariana Perepitchka - mperepitchka@u.northwestern.edu, Yekaterina Galat - ygalat@luriechildrens.org, and Vasiliy Galat - v-galat@northwestern.edu
Abstract
Trisomy 21 (T21), known as Down syndrome (DS), is a widely studied chromosomal abnormality. Previous studies have shown that DS individuals have a unique cancer profile. While exhibiting low solid tumor prevalence, DS patients are at risk for hematologic cancers, such as acute megakaryocytic leukemia and acute lymphoblastic leukemia. We speculated that endothelial cells are active players in this clinical background. To this end, we hypothesized that impaired DS endothelial development and functionality, impacted by genome-wide T21 alterations, potentially results in a suboptimal endothelial microenvironment with the capability to prevent solid tumor growth.
To test this hypothesis, we assessed molecular and phenotypic differences of endothelial cells differentiated from Down syndrome and euploid iPS cells. Microarray, RNA-Seq, and bioinformatic analyses revealed that most significantly expressed genes belong to angiogenic, cytoskeletal rearrangement, extracellular matrix remodeling, and inflammatory pathways. Interestingly, the majority of these genes are not located on Chromosome 21. To substantiate these findings, we carried out functional assays. The obtained phenotypic results correlated with the molecular data and showed that Down syndrome endothelial cells exhibit decreased proliferation, reduced migration, and a weak TNF-α inflammatory response. Based on this data, we provide a set of genes potentially associated with Down syndrome’s elevated leukemic incidence and its unfavorable solid tumor microenvironment—highlighting the potential use of these genes as therapeutic targets in translational cancer research.
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27712
Press release - https://www.oncotarget.com/news/pr/down-syndrome-ipsc-model-an-endothelial-perspective-on-tumor-development/
Keywords - Down syndrome, iPSC-derived endothelial model, T21 genome-wide Implications, meta-analysis, tumor microenvironment
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
BUFFALO, NY-March 22, 2022 – Impact Journals publishes scholarly journals in biomedical sciences with a focus on all areas of cancer and aging research. Impact Journals will be participating as an exhibitor at the American Association for Cancer Research (AACR) 2022 annual meeting from April 8-13, 2022, in New Orleans, Louisiana. This year, the AACR conference is entitled, “Decoding Cancer Complexity | Integrating Science | Transforming Patient Outcomes.”
Oncotarget and Aging (Aging-US) are Impact Journals' two most prominent journals. Oncotarget is a peer-reviewed, open-access journal dedicated to publishing high-quality, primarily oncology-focused research—in a continuous format within ongoing yearly volumes. Aging is a twice-monthly, traditional, peer-reviewed, open-access journal covering all areas of research on aging, including age-related diseases such as cancer and COVID-19.
Visit booth No. 2012 at the 2022 AACR annual meeting from April 8-13, 2022, to connect with members of the Impact Journals team.
To learn more about Impact Journals, visit www.ImpactJournals.com.
For media requests, please contact media@impactjournals.com.
Follow us on social media: Oncotarget Twitter – https://twitter.com/Oncotarget Oncotarget Facebook – https://www.facebook.com/Oncotarget Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Aging YouTube – https://www.youtube.com/agingus Aging LinkedIn – https://www.linkedin.com/company/aging Aging SoundCloud – https://soundcloud.com/aging-us
Impact Journals LLC 6666 E.Quaker St. Ste. 1 Orchard Park, NY 14127
Listen to a blog summary of a trending research paper published in Volume 13, entitled, “Correlation of nuclear pIGF-1R/IGF-1R and YAP/TAZ in a tissue microarray with outcomes in osteosarcoma patients.” __________________________
Osteosarcoma (OS) is a fairly uncommon type of bone cancer that primarily develops in the long bones found in the arms and legs. While most osteosarcomas occur in patients between the ages of 10 and 30 years old, half of all osteosarcomas develop in children. Osteosarcoma is a genetically diverse cancer that lacks a consistent targetable mutation—saddling patients and researchers with major challenges when it comes to treatment options.
“Despite their high mutation burden, OS has proven surprisingly recalcitrant to the numerous immunotherapies that have revolutionized the treatment of other mutation-high cancers.”
The lack of consistent therapeutic targets in osteosarcoma has driven researchers to investigate the role of oncogenic signaling pathways in this disease. In a trending research paper published in Oncotarget on March 9, 2022, researchers from The University of Texas’ MD Anderson Cancer Center and Rice University evaluated osteosarcoma and two cancer-related signaling pathways: IGF-1/mTOR and YAP/TAZ (the Hippo Pathway). Their paper was entitled, “Correlation of nuclear pIGF-1R/IGF-1R and YAP/TAZ in a tissue microarray with outcomes in osteosarcoma patients.”
Full blog - https://www.oncotarget.org/2022/03/24/trending-with-impact-interrelated-oncogenic-pathways-in-osteosarcoma/
DOI - https://doi.org/10.18632/oncotarget.28215
Correspondence to - Joseph A. Ludwig - jaludwig@mdanderson.org, and Antonios G. Mikos - mikos@rice.edu
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28215
Keywords - osteosarcoma, YAP/TAZ, IGF-1R, nuclear IGF-1R, mechanotransduction
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to a blog summary of a trending research paper published by Oncotarget in Volume 13, entitled, "Transplantation of autologous bone marrow pre-loaded ex vivo with oncolytic myxoma virus is efficacious against drug-resistant Vk*MYC mouse myeloma.“ ______________________
Multiple myeloma (MM) is a currently incurable cancer of blood plasma cells. Autologous stem cell transplantation (ASCT) has had efficacious results among eligible patients. However, even after ASCT, a significant number of patients continue to relapse and become resistant to current standard therapies.
A promising new method to treat blood cancers is a form of immunotherapy called virotherapy. Oncolytic viruses are uniquely capable of being reprogrammed to selectively infect and kill various cancer cells without infecting or damaging normal cells in host organisms, including mice and humans. Researchers from Arizona State University, Emory University and the Mayo Clinic (in Scottsdale, Arizona) had previously experimented with using the oncolytic myxoma virus (MYXV) to treat MM. In nature, MYXV only affects rabbits and is innocuous in mice and humans. They found that MYXVs delivered through stem cell transplantation can eliminate some residual MM cells in the Balb/c mouse model.
“Recently, we reported that ex vivo virotherapy with oncolytic myxoma virus (MYXV) improved MM-free survival in an autologous-transplant Balb/c mouse model.”
However, the researchers found that Balb/c mice may not be ideal models for MM. They observed that the behavior of MM in Balb/c mice did not quite reflect the development, clinical manifestation and localization of MM observed in human patients. Therefore, the team conducted a new study of MYXVs in the VkMYC transplantable C57BL/6 mouse MM model. Their trending research paper was published in Oncotarget on March 3, 2022, and entitled, “Transplantation of autologous bone marrow pre-loaded ex vivo with oncolytic myxoma virus is efficacious against drug-resistant VkMYC mouse myeloma.“
Full blog post - https://www.oncotarget.org/2022/03/17/trending-with-impact-adjunct-virotherapy-fights-multiple-myeloma/
DOI - https://doi.org/10.18632/oncotarget.28205
Correspondence to - Grant McFadden - grantmcf@asu.edu
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28205
Keywords - myxoma virus, multiple myeloma, combination therapy, autologous transplantation, oncolytic virus
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to a blog summary of a trending editorial co-authored by researchers Jennifer Y. Sheng and Vered Stearns from Johns Hopkins School of Medicine and the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, entitled, "Innovating and expanding weight loss strategies for breast cancer survivors.” ___
After being diagnosed with breast cancer, up to 96% of women have reported gaining weight. Medications, inactivity, food choice, and food quantity can all lead to weight gain. Studies have shown that weight gain can increase the risk of breast cancer recurrence by 40–50% and breast cancer-related mortality by 53–60%. Thus, for women with breast cancer and those who have survived breast cancer, weight management is a potentially life-saving intervention.
In an editorial paper published by Oncotarget in 2021, researchers Jennifer Y. Sheng and Vered Stearns from Johns Hopkins School of Medicine and the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center discussed the results of the 2020 POWER-Remote Trial—a study among breast cancer survivors on the results of a remote-based weight loss program compared with a self-directed approach. Their editorial paper is entitled, “Innovating and expanding weight loss strategies for breast cancer survivors.”
THE POWER INTERVENTION The Practice-based Opportunities for Weight Reduction (POWER) intervention is a 12-week behavioral weight loss program designed for overweight and obese participants. The POWER program strategy focuses on physical activity and behavioral changes, nutrition education and setting individual goals. Researchers developed the POWER-remote intervention to enable participants to engage in this weight loss program remotely through weekly video conferences and phone calls. In the current editorial paper, the researchers discussed the results from a study that adapted the POWER-remote intervention for breast cancer survivors: the POWER-Remote Trial.
“The original Practice-based Opportunities for Weight Reduction (POWER) study in obese individuals with a risk for cardiovascular disease demonstrated equivalent weight loss outcomes between in-person coaching and a remote intervention.”
Full blog - https://www.oncotarget.org/2022/03/09/a-remote-weight-loss-strategy-for-breast-cancer-survivors/
DOI - https://doi.org/10.18632/oncotarget.27898 (PDF Download)
Full text - https://www.oncotarget.com/article/27898/
Correspondence to - Jennifer Y. Sheng - jsheng7@jhmi.edu
Author interview - https://www.youtube.com/watch?v=8owrnhxzq7A
Author testimonial - https://www.youtube.com/watch?v=Cb8GR__ILMo
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27898
Press release - https://www.oncotarget.com/news/pr/innovating-expanding-weight-loss-strategies-for-breast-cancer-survivors/
Keywords - breast cancer, obesity, lifestyle interventions
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
The genetic changes that occur within the protein-coding gene NOTCH1 have not yet been fully studied or classified. Despite a lack in research, previous studies have suggested that NOTCH1 may be a potential target for novel cancer therapies, particularly against triple-negative breast cancer (TNBC). NOTCH1 variants in TNBC tend to cluster in the PEST region and have previously been linked to gamma secretase inhibitor (GSI) sensitivity and chemotherapy resistance.
“Furthermore, TNBC patients with increased Notch1 expression have demonstrated increased aggressive phenotypes and lower median overall survival [25].”
Since TNBC is well-known for a lack of actionable therapeutic targets, aggressive phenotypes and poor prognoses, there is an important need to develop new targeted therapies—as well as predictive markers for those therapies. Researchers from The Johns Hopkins University School of Medicine, Vanderbilt University Medical Center and The Vanderbilt-Ingram Cancer Center experimented in vitro with NOTCH1 variants and their ability to predict TNBC responsiveness to GSIs and standard of care chemotherapies. Their trending research paper was published by Oncotarget on February 16, 2022, and entitled, “NOTCH1 PEST domain variants are responsive to standard of care treatments despite distinct transformative properties in a breast cancer model.”
Full blog - https://www.oncotarget.org/2022/02/24/trending-with-impact-are-notch1-variants-prognostic-in-breast-cancer/
DOI - https://doi.org/10.18632/oncotarget.28200
Correspondence to - Ben Ho Park - ben.h.park@vumc.org
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28200
Keywords - NOTCH1, TNBC, breast cancer, PEST
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Franco Cortese from the Biogerontology Research Foundation, London, UK, details a review he co-authored that was published by Oncotarget in Volume 9, Issue 18, entitled, “Vive la radiorésistance!: converging research in radiobiology and biogerontology to enhance human radioresistance for deep space exploration and colonization.”
DOI - https://doi.org/10.18632/oncotarget.24461
Correspondence to - Ivan V. Ozerov - ivan@insilicomedicine.com, Morten Scheibye-Knudsen - mscheibye@sund.ku.dk, and Alex Zhavoronkov - alex@insilico.com
Abstract
While many efforts have been made to pave the way toward human space colonization, little consideration has been given to the methods of protecting spacefarers against harsh cosmic and local radioactive environments and the high costs associated with protection from the deleterious physiological effects of exposure to high-Linear energy transfer (high-LET) radiation. Herein, we lay the foundations of a roadmap toward enhancing human radioresistance for the purposes of deep space colonization and exploration. We outline future research directions toward the goal of enhancing human radioresistance, including upregulation of endogenous repair and radioprotective mechanisms, possible leeways into gene therapy in order to enhance radioresistance via the translation of exogenous and engineered DNA repair and radioprotective mechanisms, the substitution of organic molecules with fortified isoforms, and methods of slowing metabolic activity while preserving cognitive function. We conclude by presenting the known associations between radioresistance and longevity, and articulating the position that enhancing human radioresistance is likely to extend the healthspan of human spacefarers as well.
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.24461
Keywords - radioresistance, space exploration, longevity, DNA damage, Mars mission
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Dr. Dae Joon Kim and Liza Morales from the Department of Biomedical Sciences, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX, detail a priority research paper they co-authored that was published by Oncotarget in Volume 8, Issue 53, entitled, “UVB-induced nuclear translocation of TC-PTP by AKT/14-3-3σ axis inhibits keratinocyte survival and proliferation.”
DOI - https://doi.org/10.18632/oncotarget.21794
Correspondence to - Dae Joon Kim - dae.kim@utrgv.edu
Abstract
Understanding protein subcellular localization is important to determining the functional role of specific proteins. T-cell protein tyrosine phosphatase (TC-PTP) contains bipartite nuclear localization signals (NLSI and NLSII) in its C-terminus. We previously have demonstrated that the nuclear form of TC-PTP (TC45) is mainly localized to the cytoplasm in keratinocytes and it is translocated to the nucleus following UVB irradiation. Here, we report that TC45 is translocated by an AKT/14-3-3σ-mediated mechanism in response to UVB exposure, resulting in increased apoptosis and decreased keratinocyte proliferation. We demonstrate that UVB irradiation increased phosphorylation of AKT and induced nuclear translocation of 14-3-3σ and TC45. However, inhibition of AKT blocked nuclear translocation of TC45 and 14-3-3σ. Site-directed mutagenesis of 14-3-3σ binding sites within TC45 showed that a substitution at Threonine 179 (TC45/T179A) effectively blocked UVB-induced nuclear translocation of ectopic TC45 due to the disruption of the direct binding between TC45 and 14-3-3σ. Overexpression of TC45/T179A in keratinocytes resulted in a decrease of UVB-induced apoptosis which corresponded to an increase in nuclear phosphorylated STAT3, and cell proliferation was higher in TC45/T179A-overexpressing keratinocytes compared to control keratinocytes following UVB irradiation. Furthermore, deletion of TC45 NLSII blocked its UVB-induced nuclear translocation, indicating that both T179 and NLSII are required. Taken together, our findings suggest that AKT and 14-3-3σ cooperatively regulate TC45 nuclear translocation in a critical step of an early protective mechanism against UVB exposure that signals the deactivation of STAT3 in order to promote keratinocyte cell death and inhibit keratinocyte proliferation.
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.21794
Keywords - TC-PTP, nuclear translocation, AKT, 14-3-3σ, keratinocytes
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Acute myeloid leukemia (AML) is a cancer of the blood that begins in the bone marrow and progresses quickly if left untreated. AML can occur both in adults and children and is often treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT is a procedure that replaces stem cells that were damaged or destroyed after radiation and/or chemotherapy treatment with stem cells from healthy donors. While allo-HSCT provides a high rate of curability in AML patients, the success of this procedure is partially dependent on the efficacy of pre-transplant treatment regimens. Researchers have identified an urgent need to determine new therapeutic approaches that provide better cytotoxicity in AML cells, without jeopardizing patient safety.
To improve AML patient outcomes after allo-HSCT, researchers from the University of Texas MD Anderson Cancer Center and the University of Alberta’s Cross Cancer Institute conducted a new study investigating the combinations of the BCL-inhibitor ABT199/venetoclax with two alkylating agents and a nucleoside analog. Their trending research paper was published by Oncotarget on February 10, 2022, and entitled, “ABT199/venetoclax potentiates the cytotoxicity of alkylating agents and fludarabine in acute myeloid leukemia cells.”
“One such candidate drug is ABT199/venetoclax, a BH3-mimetic small molecule that binds to and inhibits the anti-apoptotic B-cell lymphoma 2 (BCL2) protein, preferentially causing malignant cells to undergo apoptosis.”
Full blog - https://www.oncotarget.org/2022/02/17/trending-with-impact-new-pre-transplant-aml-treatment-combinations/
DOI - https://doi.org/10.18632/oncotarget.28193
Correspondence to - Benigno C. Valdez - bvaldez@mdanderson.org
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28193
Keywords - ABT199/venetoclax, busulfan, cyclophosphamide, fludarabine, acute myeloid leukemia
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Dr. Bishal Gyawali from the Institute of Cancer Policy, London and Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, discusses an editorial he authored that was published by Oncotarget in Volume 8, Issue 52, entitled, “Cancer drugs in LMICs: cheap but unaffordable.”
DOI - https://doi.org/10.18632/oncotarget.21976 (PDF download)
Full text - https://www.oncotarget.com/article/21976/
Correspondence to - Bishal Gyawali - bg.bishalgyawali@gmail.com; https://twitter.com/oncology_bg
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.21976
Keywords - value, affordability, global oncology, drug prices, cancer
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Iron is essential for human life, however, this element can also become toxic in high doses. Contrary to iron anemia, iron overload occurs when the body accumulates more iron than it can use, and this excess iron is damaging to cells and tissues. Famous for their atypical growth patterns, cancer cells accumulate a surplus of iron to support their irregular growth and metabolism. Thus, the metabolism of cancer cells may be exploited by targeting their proclivity to require and retain iron.
“Iron chelators selectively deplete cancer cells of iron, exploiting cancer’s iron addiction – a trait displayed by a range of different cancers.”
Iron chelators are compounds that can bind to iron and facilitate iron wasting. Depriving the body of iron using iron chelators has selectively cytotoxic effects in cancer cells. Some natural iron chelators include turmeric, quercetin, resveratrol, and green tea. Synthetic iron chelators include derivatives of 8-hydroxyquinoline, tachpyridine and deferoxamine. A considerable number of studies have shown that iron chelators can reverse some major catalysts and hallmarks of cancer—making iron chelators a promising treatment option for cancer patients.
Researchers Gina Abdelaal and Stephany Veuger from Northumbria University reviewed the available research literature about the impact of iron chelation on cancer cell survival and the underlying mechanisms of action. Their review paper was published by Oncotarget in 2021 and entitled, “Reversing oncogenic transformation with iron chelation.”
Full blog - https://www.oncotarget.org/2022/02/10/iron-chelators-in-cancer-treatment/
DOI - https://doi.org/10.18632/oncotarget.27866
Correspondence to - Gina Abdelaal - gina.abdelaal@northumbria.ac.uk
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27866
Press release - https://www.oncotarget.com/news/pr/reversing-oncogenic-transformation-with-iron-chelation/
Keywords - iron chelator, oncogenesis, selective cytotoxicity, hallmarks of cancer, NDRG1
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Dr. Derrick Haslem and Dr. Lincoln Nadauld from the Precision Genomics Program, Intermountain Healthcare, Saint George, UT, discuss a research paper they co-authored that was published by Oncotarget as the cover for Volume 9, Issue 15, entitled, “Precision oncology in advanced cancer patients improves overall survival with lower weekly healthcare costs.”
DOI - https://doi.org/10.18632/oncotarget.24384
Correspondence to - Lincoln D. Nadauld - lincoln.nadauld@imail.org
Abstract The impact of precision oncology on guiding treatment decisions of late-stage cancer patients was previously studied in a retrospective analysis. However, the overall survival and costs were not previously evaluated. We report the overall survival and healthcare costs associated with precision oncology in these patients with advanced cancer. Building on a matched cohort study of 44 patients with metastatic cancer who received all of their care within a single institution, we evaluated the overall survival and healthcare costs for each patient. We analyzed the outcomes of 22 patients who received genomic testing and targeted therapy (precision oncology) between July 1, 2013 and January 31, 2015, and compared to 22 historically controlled patients (control) who received standard chemotherapy (N = 17) or best supportive care (N = 5). The median overall survival was 51.7 weeks for the targeted treatment group and 25.8 weeks for the control group (P = 0.008) when matching on age, gender, histological diagnosis and previous treatment lines. Average costs over the entire period were $2,720 per week for the targeted treatment group and $3,453 per week for the control group, (P = 0.036). A separate analysis of 1,814 patients with late-stage cancer diagnoses found that those who received a targeted cancer treatment (N = 93) had 6.9% lower costs in the last 3 months of life compared with those who did not. These findings suggest that precision oncology may improve overall survival for refractory cancer patients while lowering average per-week healthcare costs, resource utilization and end-of-life costs.
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.24384
Press release - https://www.oncotarget.com/news/pr/precision-oncology-in-advanced-cancer-patients-improves-overall-survival-with-lower-weekly-healthcare-costs/
Keywords - precision medicine, oncology, outcomes, costs, overall survival
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Adrenocortical carcinoma (ACC) is a rare and aggressive cancer that forms in the outer layer of the adrenal gland tissue above the kidneys. According to the National Institutes of Health, the occurrence of ACC in the United States is believed to only affect one to two people per million, per year. This highly-rare disease also challenges patients and researchers due to its post-diagnosis five-year survival rate of a mere 51%.
At this time, there are no known external factors that cause this disease. Most adrenocortical tumors that have been found produce symptoms including abdominal pain and higher levels of certain hormones, inclusive of cortisol, aldosterone, testosterone, and estrogen. Any of these hormones produced in excess can have numerous troubling effects on the body and, most alarmingly, the cancer cells in the adrenal glands have the potential to travel to other organs.
Researchers—from the National Cancer Institute, Stanford University, Medical College of Wisconsin, Frederick National Laboratory for Cancer Research, and Salubris Biotherapeutics—conducted a study to learn more about ACC and the mechanisms that lead to the biological materialization of this ultra-rare disease. In 2020, their research paper was published by Oncotarget and entitled, “GATA3 and APOBEC3B are prognostic markers in adrenocortical carcinoma and APOBEC3B is directly transcriptionally regulated by GATA3.”
Full blog - https://www.oncotarget.org/2022/01/26/study-demonstrates-excess-of-protein-is-regulated-by-gata3-in-ultra-rare-adrenal-cancer/
DOI - https://doi.org/10.18632/oncotarget.27703
Correspondence to - Electron Kebebew - kebebew@stanford.edu
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27703
Press release - https://www.oncotarget.com/news/pr/gata3-and-apobec3b-are-prognostic-markers-in-adrenocortical-carcinoma-and-apobec3b-is-directly-transcriptionally-regulated-by-gata3/
Keywords - adrenocortical carcinoma, APOBEC3B, GATA3, prognosis, DNA damage
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A type of mental fog—known as “chemo brain”—is widely experienced by patients who have undergone cancer treatment. Cancer research institutions define chemo brain as impaired cognition, including cloudiness, memory loss and/or lack of concentration, that occurs before, during and/or after cancer treatment. This condition can negatively impact quality of life in a significant way. Chemo brain not only affects recovering individuals but also their loved ones, who often must take on additional caregiving responsibilities. Despite the name, chemotherapeutic drugs may not be the only treatments responsible for chemo brain.
A chemotherapy protective drug called amifostine is commonly used in patients and paired with chemotherapeutic agents. Amifostine functions to protect healthy cells from DNA double strand breaks (DSBs) induced by chemotherapy. Another commonly prescribed cancer treatment is called etoposide, which is a chemotherapeutic drug that also targets DSBs. Etoposide, on the other hand, functions to increase DSBs in cancer cells. Recently, researchers have suggested that DSBs could play a role in learning, memory and immediate early gene (IEG) expression. The activity of IEGs can be used to identify neural circuits involved in learning and memory processes.
“Despite their wide clinical use, there is little information about how amifostine and etoposide affect learning and memory.”
Researchers from Oregon Health and Science University conducted a novel study to observe the isolated effects of these common DSB-altering agents on learning, memory and IEG expression. Systemic injections of amifostine and etoposide were examined in both male and female mice. Their research paper was published by Oncotarget in January of 2022, and entitled, “Common cancer treatments targeting DNA double strand breaks affect long-term memory and relate to immediate early gene expression in a sex-dependent manner.”
Full blog - https://www.oncotarget.org/2022/01/28/trending-with-impact-what-causes-chemo-brain/
DOI - https://doi.org/10.18632/oncotarget.28180
Correspondence to - Jacob Raber - raberj@ohsu.edu
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28180
Keywords - amifostine, etoposide, double strand breaks, memory, sex
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Dr. Nerymar Ortiz-Otero from the Meinig School of Biomedical Engineering, Cornell University, discusses a research paper she co-authored that was published by Oncotarget in Volume 11, Issue 12, entitled, “Cancer associated fibroblasts confer shear resistance to circulating tumor cells during prostate cancer metastatic progression.”
DOI - https://doi.org/10.18632/oncotarget.27510
Correspondence to - Michael R. King - mike.king@vanderbilt.edu
Abstract Previous studies have demonstrated that CTCs do not travel in the bloodstream alone, but rather are accompanied by clusters of stromal cells such as cancer associated fibroblasts (CAFs). Our laboratory has confirmed the presence of CAFs in the peripheral blood of prostate cancer (PC) patients. The observation that CAFs disseminate with CTCs prompts the examination of the role of CAFs in CTC survival under physiological shear stress during the dissemination process using a clinically relevant, three-dimensional (3D) co-culture model. In this study, we found that “reactive CAFs” induce shear resistance to prostate tumor cells via intercellular contact and soluble derived factors. In addition, these reactive CAFs conserve the proliferative capability of tumor cells in the presence of high magnitude fluid shear stress (FSS). This reactive CAF phenotype emerges from normal fibroblasts (NF), which take on the CAF phenotype when co-cultured with tumor cells. The reactive CAFs showed higher expression of α-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP) compared to differentiated CAFs, when co-cultured with PC cells at the same experimental conditions. Together, we found that the activation mechanism of NF to CAF comprises different stages that progress from a reactive to quiescent cellular state in which these two states are differentiated by the fluctuation of intensity in CAF markers. Here we determined that a reactive state of CAFs proved to be important for supporting tumor cell survival and proliferation. These findings suggest the use of CAFs as a marker for cancer progression and a potential target for novel cancer therapeutics to treat metastatic disease.
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27510
Press release - https://www.oncotarget.com/news/pr/cancer-associated-fibroblasts-confer-shear-resistance-to-circulating-tumor-cell/
Keywords - metastasis, cancer associated fibroblasts, circulating tumor cells, cytoprotection, collective migration
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to a list of the 10 most-viewed oncology-focussed papers on Oncotarget.com in 2021.
10 - “Metformin and berberine, two versatile drugs in treatment of common metabolic diseases” DOI - https://doi.org/10.18632/oncotarget.20807
9 - “Cell fusion as a link between the SARS-CoV-2 spike protein, COVID-19 complications, and vaccine side effects” https://doi.org/10.18632/oncotarget.28088
8 - “Physical activity and telomere length: Impact of aging and potential mechanisms of action” https://doi.org/10.18632/oncotarget.16726
7 - “Hedgehog signaling induces PD-L1 expression and tumor cell proliferation in gastric cancer” https://doi.org/10.18632/oncotarget.26473
6 - “cGAS-STING pathway in oncogenesis and cancer therapeutics” https://doi.org/10.18632/oncotarget.27673
5 - “Anti-aging: senolytics or gerostatics (unconventional view)” https://doi.org/10.18632/oncotarget.28049
4 - “Melatonin increases overall survival of prostate cancer patients with poor prognosis after combined hormone radiation treatment” https://doi.org/10.18632/oncotarget.27757
3 - “Scent test using Caenorhabditis elegans to screen for early-stage pancreatic cancer” https://doi.org/10.18632/oncotarget.28035
2 - “Inflammatory responses and inflammation-associated diseases in organs” https://doi.org/10.18632/oncotarget.23208
1 - “The goal of geroscience is life extension” https://doi.org/10.18632/oncotarget.27882
Keywords - cancer, science, research, oncology, openaccess, researchpapers, journalpublication
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget
Oncotarget is published by Impact Journals, LLC: https://www.impactjournals.com/
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Dr. J. James Frost, formerly of Johns Hopkins Department of Radiology, talks about his experience publishing the 2017 paper, “Symmetry and symmetry breaking in cancer: a foundational approach to the cancer problem,” with Oncotarget.
DOI - https://doi.org/10.18632/oncotarget.22939
Correspondence to - J. James Frost - jfrost@jhmi.edu
Keywords - cancer, symmetry, symmetry-breaking, complexity, scale-free
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Dr. Ken Pienta from Johns Hopkins School of Medicine discusses his experiences publishing numerous research papers with Oncotarget.
DOI - https://doi.org/10.18632/oncotarget.22939
Correspondence to - J. James Frost - jfrost@jhmi.edu
Keywords - cancer, symmetry, symmetry-breaking, complexity, scale-free
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Dr. Dean Felsher from Stanford University School of Medicine, Departments of Medicine and Pathology and member of Oncotarget’s Founding Editorial Board, talks about the editorial process at Oncotarget.
DOI - https://doi.org/10.18632/oncotarget.22342
Correspondence to - Dean W. Felsher - dfelsher@stanford.edu
Keywords - liver cancer, HCC, miR, MYC, lipid nanoparticle (LNP)
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Dr. Reshma Sundar and Dr. Marene Landström from the Department of Medical Biosciences at Umeå University in Sweden discuss their experience publishing the research paper, “Pro-invasive properties of Snail1 are regulated by sumoylation in response to TGFβ stimulation in cancer”, with Oncotarget in 2017.
DOI - https://doi.org/10.18632/oncotarget.20097
Correspondence to - Marene Landström - Marene.Landstrom@medbio.umu.se
Keywords - signal transduction, tumor biology, Snail1, sumoylation, prostate cancer
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Dr. Michael Andreeff with the Department of Leukemia, Section of Molecular Hematology and Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, talks about his experience publishing "Tumor Trp53 status and genotype affect the bone marrow microenvironment in acute myeloid leukemia" with Oncotarget in 2017.
DOI - https://doi.org/10.18632/oncotarget.19042
Correspondence to - Michael Andreeff - mandreef@mdanderson.org
Keywords - AML, microenvironment, GEP, stroma, genotype
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Dr. John R. Hawse with the Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, talking about his experience publishing "ERβ inhibits cyclin dependent kinases 1 and 7 in triple negative breast cancer" with Oncotarget in 2017.
DOI - https://doi.org/10.18632/oncotarget.21787
Correspondence to - John R. Hawse - hawse.john@mayo.edu
Keywords - TNBC, ERβ, cell cycle, CDK, estrogen
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Dr. Sandip Pravin Patel, Dr. Karen Yun and Dr. Karen Mccowen from the University of California San Diego, discuss a research paper they co-authored that was published by Oncotarget in Volume 11, Issue 28, entitled, “Rapid onset type 1 diabetes with anti-PD-1 directed therapy.”
DOI - https://doi.org/10.18632/oncotarget.27665
Correspondence to - Sandip Pravin Patel - patel@ucsd.edu
Abstract Type 1 diabetes is a rare immune-related adverse event (irAE) caused by checkpoint inhibitors with serious risk for diabetic ketoacidosis (DKA). Using our electronic medical record, we identified 1327 adult patients who received PD-(L)1 or CTLA-4 inhibitors from 2013 to 2018. Of the patients who received immunotherapy, 5 (0.38%) patients were found to have type 1 diabetes, all of whom presented with DKA requiring insulin at 20 to 972 days from their first anti-PD-(L)1 dose. All patients were treated with anti-PD-1 therapy (nivolumab or pembrolizumab). Four patients had new onset diabetes with mean HbA1c of 9.1% on DKA presentation and persistent elevations over time. Two patients who tested positive for glutamic acid decarboxylase (GAD) antibodies presented with DKA at 20 and 106 days from first anti-PD-1 administration whereas patients who were autoantibody negative had DKA more than a year later. Type 1 diabetes occurs within a wide time frame after anti-PD-1 initiation and commences with an abrupt course. Our case series suggests that monitoring glycemia in patients on PD-1 inhibitors is not predictive for diabetes occurrence. GAD autoantibodies could portend earlier onset for diabetes, although further prospective studies are needed to elucidate their diagnostic utility and contribution in therapeutic interception.
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27665
Press release - https://www.oncotarget.com/index.php?journal=oncotarget&page=news&op=press&item=oncotarget-rapid-onset-type-1-diabetes-with-anti-pd-1-directed-therap
Keywords - type 1 diabetes, diabetic ketoacidosis (DKA), immune-related adverse event (irAE), immunotherapy, PD-1 inhibitors
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC: https://www.ImpactJournals.com
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Dr. Sridhar Mani from Medicine and Genetics of The Albert Einstein College of Medicine, Bronx, NY, details his editorial published by Oncotarget in Volume 11, Issue 19, entitled, “Microbial metabolite mimicry: one step closer to drug discovery.”
DOI - https://doi.org/10.18632/oncotarget.27591
Correspondence to - Sridhar Mani - sridhar.mani@einsteinmed.org
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27591
Keywords - microbial metabolites, inflammation, IBD, mimicry, drugs
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Head and neck cancer is a group of various tumors located in the oral cavity, oropharynx, larynx, and hypopharynx. Head and neck cell squamous-cell carcinomas (HNSCC) often result from tobacco use or human papillomavirus (HPV+) infection. In locally advanced HNSCC, the current therapies used are combined surgery, radiotherapy and chemotherapy. Despite the use of traditional treatments, up to 50% of patients relapse due to the increase in mutational burden as HNSCC advances. Few studies have investigated the therapeutic potential of neoantigens in HNSCC tumors.
“Prior work has characterized changes in the mutation burden between primary and recurrent tumors; however, little work has characterized the changes in neoantigen evolution.”
Neoantigens are new proteins/antigens that form on cancer cells after mutations occur in the tumor DNA. Certain neoantigens can promote anti-tumor immune responses and are potentially capable of controlling tumor progression. In an effort to characterize genomic and neoantigen changes in patients with HNSCC, researchers—from Washington University in St. Louis, Columbia University, St. Louis Children’s Hospital, and Siteman Cancer Center—investigated 23 paired primary and recurrent HNSCC tumors. Their paper, entitled, “Genomic and neoantigen evolution from primary tumor to first metastases in head and neck squamous cell carcinoma,” was chosen as the cover paper for Oncotarget’s Volume 12, Issue #6.
Full blog -https://www.oncotarget.org/2022/01/13/primary-versus-metastatic-head-and-neck-tumors/
Press release - https://www.oncotarget.com/news/pr/genomic-and-neoantigen-evolution-in-head-and-neck-squamous-cell-carcinoma/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27907
DOI - https://doi.org/10.18632/oncotarget.27907
Full text - https://www.oncotarget.com/article/27907/text/
Correspondence to - Brian A. Van Tine - bvantine@wustl.edu
Keywords - head and neck squamous cell carcinoma, neoantigens, mutational evolution, tumor relapse, immune cell infiltration
About Oncotarget:
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit www.oncotarget.com or follow us:
SoundCloud - @oncotarget Facebook - www.facebook.com/Oncotarget/ Twitter - twitter.com/oncotarget LinkedIn - www.linkedin.com/company/oncotarget Instagram - www.instagram.com/oncotargetjrnl/ YouTube - www.youtube.com/OncotargetYouTube Pinterest - www.pinterest.com/oncotarget/ Reddit - www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
BUFFALO, NY, January 6, 2022 – Since its inception in 2010, Oncotarget has operated as a traditional-style journal that publishes online page numbered issues of peer-reviewed papers. Final paginated issues were then released in their permanent form to Pubmed.
As of 2022, Oncotarget has shifted to a continuous publishing model. Papers will now be published continuously within yearly volumes in their final and complete form. This means that qualified, rigorously peer-reviewed articles will be published online as soon as they are in their fully formatted and final version of record. With continuous publication, articles posted online are complete with citation details and are available in full text html and PDF formats. Additionally, research papers will appear on PubMed quickly—just days after the papers are published by Oncotarget.
Why the change? In an increasingly digital world, the open-access continuous publishing model is ideal for authors, researchers and overall readership. Continuous publishing allows for faster research dissemination, citation and clinical application, compared to a traditional format.
Oncotarget is committed to doing our part to ensure that research is available to the biomedical community as quickly as possible, while maintaining high standards of quality.
To learn more about Oncotarget, visit Oncotarget.com or connect with us on social media:
Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA
About Impact Journals (Oncotarget’s publisher):
Impact Journals is a New York-based open-access publisher with a mission to provide scientists with the opportunity to share their exceptional discoveries, and to present vital findings from different fields of biomedical science. Our goal is life without disease.
For media inquiries, please contact media@impactjournals.com.
Statistics from the American Cancer Society indicate that endometrial cancer (EC) is on the rise among women in the United States. While it more commonly affects older women, researchers are finding that EC is the only gynecological cancer today increasing in incidence and mortality among younger women. Not to be confused with the benign condition of endometriosis, EC tumors are highly heterogeneous and are a challenge to diagnose and treat. Since these heterogeneous tumors also develop in differential growing environments, most studies that use EC cell lines to diagnose patients or develop treatments do not translate to efficacy in vivo.
“Current methodologies for diagnosis and treatment rely on the use of cell lines as models for tumor biology. However, due to inherent heterogeneity and differential growing environments between cell lines and tumors, these comparative studies have found little parallels in molecular signatures.”
In a new study, researchers from the Uniformed Services University of the Health Sciences and the National Institutes of Health compared signaling pathways and genes among EC cell lines and tumors in The Cancer Genome Atlas (TCGA). Their goal was to identify parallels between cell lines and tumors that may be associated with regulating EC transformation and progression. In December 2021, their research paper was published as the cover of Oncotarget’s Volume 12, Issue 26, and entitled, “Comparative transcriptome analysis between patient and endometrial cancer cell lines to determine common signaling pathways and markers linked to cancer progression”.
“Identifying mutually dysregulated biomarkers and signaling pathways in cell lines and tumors can advantageously provide a more expedient method for studying mechanisms in cancer biology.”
Full blog - https://www.impactjournals.com/journals/blog/oncotarget/new-study-biomarkers-linked-to-the-progression-of-endometrial-cancer/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28161
DOI - https://doi.org/10.18632/oncotarget.28161
Full text - https://www.oncotarget.com/article/28161/text/
Correspondence to - T. John Wu - twu@usuhs.edu
Keywords - endometrial cancer, cancer stage, comparative transcriptome analysis, signaling pathways, normalization
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget published "Host targeted antiviral (HTA): functional inhibitor compounds of scaffold protein RACK1 inhibit herpes simplex virus proliferation" which reported that due to the small number of molecular targets in viruses and the rapid evolution of viral genes, it is very challenging to develop specific antiviral drugs.
In addition, HIV-1 and Herpes Simplex virus are known to use IRES as well. By utilizing the crystal structure of the RACK1A protein from the model plant Arabidopsis and using a structure based drug design method, dozens of small compounds were identified that could potentially bind to the experimentally determined functional site of the RACK1A protein.
Dr. Sivanesan Dakshanamurthy from The Georgetown University Medical Center, Dr. Qiyi Tang from The Howard University College of Medicine and Dr. Hemayet Ullah from Howard University said, "With the small number of molecular targets in viruses and the rapid evolution of viral genes, it is very challenging to develop specific antiviral drugs."
Full press release - https://www.oncotarget.com/news/pr/functional-inhibitor-compounds-inhibit-herpes-simplex-virus-proliferation/
DOI - https://doi.org/10.18632/oncotarget.26907
Full text - https://www.oncotarget.com/article/26907/text/
Correspondence to - Sivanesan Dakshanamurthy - sd233@georgetown.edu, Qiyi Tang - qiyi.tang@howard.edu, and Hemayet Ullah - hullah@howard.edu
Keywords - host targeted antiviral (HTA), herpes simplex virus (HSV), receptor for activated C kinase 1 (RACK1), RACK1 inhibitor, internal ribosomal entry site (IRES)
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
The cover for issue 29 of Oncotarget features Figure 2, "Categorisation of samples analysed," from Laes, et al.
- OncoDNA treatment recommendation followed in 60% of cases
- 93% of treatment decisions were made based on a holistic approach combining next generation sequencing (NGS) and multiple biomarker analysis provided by OncoDNA
- 27% of late-stage patients treated with OncoDNA-recommended therapies had overall survival less than 12 months, compared to a typical average of no more than six months
Gosselies, Belgium - April 17, 2018: OncoDNA ("OncoDNA or "the Company"), the healthcare technology company that collates and translates complex cancer biomarker data to make precision medicine a reality, is pleased to announce the publication of a study in the journal Oncotarget evaluating the utility of OncoDNA's comprehensive biomarker analysis and interpretation services in clinical settings.
The study, published online today and titled "The clinical impact of using complex molecular profiling strategies in routine oncology practice", found that combining advanced, comprehensive testing of cancer biomarkers with OncoDNA's proprietary cancer treatment knowledge database can enable oncologists to make better treatment decisions for their patients. This is because OncoDNA's testing combines immunohistochemistry, next generation sequencing (NGS), and other tests including inherited heart condition testing, DNA methylation, and microsatellite instability (MSI) testing, rather than the industry standard of NGS testing alone.
Full press release - https://www.oncotarget.com/news/pr/oncodna-announces-publication-of-peer-reviewed-study-in-oncotarget-assessing-the-utility-of-its-unique-biomarker-analysis-and-interpretation-platform-in-clinical-decision-making/
DOI - https://doi.org/10.18632/oncotarget.24757
Full text - https://www.oncotarget.com/article/24757/text/
Correspondence to - Jean-François Laes - jf.laes@oncodna.com
Keywords - molecular profiling, solid tumour, precision medicine, next-generation sequencing, therapeutic decision making in oncology
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget published "Genomic and neoantigen evolution from primary tumor to first metastases in head and neck squamous cell carcinoma" which reported that prior work has characterized changes in the mutation burden between primary and recurrent tumors; however, little work has characterized the changes in neoantigen evolution.
These authors characterized genomic and neoantigen changes between 23 paired primary and recurrent head and neck squamous cell carcinoma (HNSCC) tumors.
Within these tumors, they identified 6 genes which have predicted neoantigens in 4 or more patients.
Within HNSCC tumors examined in this Oncotarget research paper, there are neoantigens in shared genes by a subset of patients.
The presence of neoantigens in these shared genes may promote an anti-tumor immune response which controls tumor progression.
Dr. Brian A. Van Tine from The Washington University in St. Louis, The St. Louis Children's Hospital as well as The Siteman Cancer Center said, "Head and neck cancer are a group of heterogeneous tumors with an estimated 644,000 new cases per year worldwide."
The infiltration of immune cells, including T cells, into tumors is associated with improved outcomes and longer survival in HNSCC.
The infiltrating T cells release granules containing perforin and granzyme A and B which directly kill tumor cells or release other cytokines and chemokines that promote the anti-tumor immune response and alter the tumor microenvironment.
For example, infiltrating T cells release interferon gamma which increases expression of PD-L1 and CTLA-4, which may increase the efficacy of immune checkpoint therapy.
Multiple studies have characterized changes in mutation burden in HNSCC, when comparing primary and metastatic tumors, no studies have characterized the shifting neoantigen burden between primary and metastatic tumors within HNSCC.
In this Oncotarget study, the authors characterized the mutational and neoantigen burden between primary and first recurrence tumors in 23 patients with HNSCC.
The Van Tine Research Team concluded in their Oncotarget Research Output that there is a shifting neoantigen burden as there are unique neoantigens in primary tumors and different unique neoantigens in the recurrent/metastatic tumors.
The patients which have these neoantigens in shared genes are patients which have higher total numbers of neoantigens.
What is clear is that patients with neoantigens in these shared genes also tend to have increased duration of survival with disease.
The increase in neoantigens and duration of survival with disease tends to be associated with increased CD3 CD8 density in the tumor and CD8A expression.
This suggests that patients with these shared neoantigens are associated with increased CD8 T cell infiltration and increased cytotoxic activity, which extends the patient's life.
DOI - https://doi.org/10.18632/oncotarget.27907
Full text - https://www.oncotarget.com/article/27907/text/
Correspondence to - Brian A. Van Tine - bvantine@wustl.edu
Keywords - head and neck squamous cell carcinoma, neoantigens, mutational evolution, tumor relapse, immune cell infiltration
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Lung cancer continues to be the leading cause of cancer deaths world-wide. Variations in the stage of diagnosis, subtypes and types of mutated genes provide a challenge for researchers who are developing targeted treatments to help rid patients of lung cancer. To this end, many researchers are interested in employing cancer-testis antigens (CTAs), which are minimally expressed in normal tissues, but strongly expressed in solid tumors. Therefore, CTAs are appealing therapeutic targets. The Kita-Kyushu lung cancer antigen-1 (also known as KK-LC-1; CT 83; CXORF61) is a CTA that is expressed in 82% of gastric tumors, 53% of breast cancers (higher in triple-negative breast cancer) and in about 33% of lung cancers.
“In lung cancer, surgical series have shown KK-LC-1 to be expressed in about one-third of lung cancer tumors [1, 3–5].”
Researchers—from the University of Southern California, Caris Life Sciences, Fox Chase Center, Georgetown Lombardi Comprehensive Cancer Center, The Warren Alpert Medical School of Brown University, Wayne State University School of Medicine, The Barbara Karmanos Cancer Institute, St. Marianna University, and the University of Utah—conducted a recent study to determine exactly which molecular subtypes of KK-LC-1 expressing lung cancer would be most responsive to a clinical trial involving the treatment of cancer with activated T lymphocytes from the body, or T cell receptor therapy (TCR-T), targeting KK-LC-1. Their research paper was published as cover of Oncotarget’s Volume 12, Issue 25, and entitled, “Molecular characterization of Kita-Kyushu lung cancer antigen (KK-LC-1) expressing carcinomas”.
Full blog - https://www.oncotarget.org/2021/12/08/lung-cancer-antigen-expression-characterized-by-molecular-subtype/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28132
DOI - https://doi.org/10.18632/oncotarget.28132
Full text - https://www.oncotarget.com/article/28132/text/
Correspondence to - Jorge J. Nieva - jorge.nieva@med.usc.edu
Keywords - lung cancer, tumor microenvironment, diagnostic biomarkers, biomarkers for immunotherapy, cancer testis antigen
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
View the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 25. https://www.oncotarget.com/archive/v12/i25/
Research Paper (Cover) - “Molecular characterization of Kita-Kyushu lung cancer antigen (KK-LC-1) expressing carcinomas” https://doi.org/10.18632/oncotarget.28132
Research Paper - “Radiomics in predicting recurrence for patients with locally advanced breast cancer using quantitative ultrasound” https://doi.org/10.18632/oncotarget.28139
Research Paper - “Beneficial effect of KYP-2047, a propyl-oligopeptidase inhibitor, on oral squamous cell carcinoma” https://doi.org/10.18632/oncotarget.28147
Editorial - “Delivering albumin-bound paclitaxel across the blood-brain barrier for gliomas” https://doi.org/10.18632/oncotarget.28018 (PDF Download)
Research Perspective - “Cell fusion as a link between the SARS-CoV-2 spike protein, COVID-19 complications, and vaccine side effects” https://doi.org/10.18632/oncotarget.28088
Keywords - lung cancer, tumor microenvironment, radiomics, breast cancer, oral squamous cell carcinoma (OSCC), glioblastoma, cell fusion, cancer, science, research, oncology
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget
Oncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget Volume 11 Issue 15 reported that several zebrafish T-ALL models have been reported, but until recently, robust D. rerio B-ALL models were not described.
Here, the Research Team has shown new B-ALL findings in one of these models, fish expressing transgenic human MYC.
They describe B-ALL incidence in a large cohort of hMYC fish, and show B-ALL in two new lines where T-ALL does not interfere with B-ALL detection.
Dr. J. Kimble Frazer from the Department of Cell Biology and the Department of Pediatrics, Section of Pediatric Hematology-Oncology, as well as the Department of Microbiology & Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA said, "Acute lymphoblastic leukemia (ALL) and the related malignancy lymphoblastic lymphoma (LBL) dominate pediatric oncology, together representing over one third of all childhood cancer."
For T-ALL in particular, zebrafish models have been highly informative, advancing our understanding of T-ALL genetics, pro- and anti-oncogenic interactions between different genes and pathways, tumor heterogeneity, leukemia stem cells, and in screens for new therapeutics.
However, despite the fact that zebrafish T-ALL models had proven to be fertile grounds for study, B-ALL modeling in D. rerio had not been fruitful, with only one low penetrance and long latency line reported.
This was curious because zebrafish recombination activating gene 2 promoters active in both immature T and B cells was used to regulate most of these transgenic oncoproteins in the various T-ALL lines, yet D. rerio B-ALL had not been reported in them.
In 2018, the zebrafish ALL field advanced suddenly with reports of B-ALL in two closely-related transgenic lines where T-ALL was already known to occur.
Here, the authors present new results in the hMYC model, including B- and T-ALL latency and penetrance data in a cohort of over 600 animals, in vivo glucocorticoid and radiation treatment of B-ALL, and expression profiles from single B- and T-ALL cells.
The Frazer Research Team concluded in their Oncotarget Research Perspective, "We postulate these and other differences may explain the apparently disparate oncogenic mechanisms employed by hMYC and mMyc in the B lymphoblasts of these closely-related lines. Pathway analysis of differentially-regulated genes predicted differing activation of several biologic pathways (e.g., cell differentiation, immune system process, lymphocyte activation, RNA binding, etc.; Figure 6B panels and Supplementary Table 4). These markedly different pathway signatures further demonstrate that human and murine MYC are far from synonymous in terms of their oncogenic effects upon zebrafish B lymphoblasts."
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27555
DOI - https://doi.org/10.18632/oncotarget.27555
Full text - https://www.oncotarget.com/article/27555/text/
Correspondence to - J. Kimble Frazer - Kimble-Frazer@ouhsc.edu
Keywords - acute lymphoblastic leukemia, ALL, zebrafish, lymphocyte, MYC
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget published "CrkL is required for donor T cell migration to GvHD target organs" which reported that the success of cancer therapies based on allogeneic hematopoietic stem cell transplant relies on the ability to separate graft-versus-host disease from graft-versus-tumor responses.
In vitro, CrkL-deficient T cells fail to polymerize actin in response to the integrin ligand ICAM-1, resulting in defective migration. In line with this, these authors found that although CrkL-deficient T cells could clear hematopoietic tumors, they failed to clear the same tumor growing subcutaneously, highlighting the role of CrkL in controlling T cell migration into peripheral tissues.
Dr. Mobin Karimi from The SUNY Upstate Medical University said, "T cell migration out of the vasculature into peripheral tissue is a key control point in the inflammatory response."
Although trafficking to tissues is required for protective immunity, uncontrolled T cell infiltration into tissue can result in exacerbated inflammation and tissue damage. T cell recruitment is highly regulated by the local endothelial cells which, in response to pro-inflammatory cues, up-regulate molecules such as chemokines and adhesion receptors. These molecules promote T cell adhesion to the endothelial monolayer, and guide migration through the monolayer into the tissue.
Activated T cells lacking Crk proteins fail to polymerize actin downstream of LFA-1, and migrate slower and less directionally than their WT counterparts. Importantly, these mutant T cells also have defects in crossing endothelial monolayers in vitro, and they fail to traffic to sites of inflammation in vivo.
Additionally, using a clinically relevant mouse model of graft-versus-host disease/graft-versus-leukemia, these authors showed that T cells lacking Crk proteins can efficiently clear tumor cells but cause little-to-no GvHD pathology. The Crk proteins are widely expressed across tissues and have many biological functions, all of which stem from their role as adaptor proteins that coordinate signaling complexes downstream of cell surface receptors.
Crk proteins are particularly important for adhesion and migration. They have been shown to localize to adhesion sites and regulate the stability of these structures in non-hematopoietic cells, and alterations in their expression are associated with invasive potential in several tumors.
The Karimi Research Team concluded in their Oncotarget Research Output, "Going forward, it will be interesting to identify CrkL binding partners and other signaling molecules needed for integrin-dependent actin responses and passage into inflamed tissues. Targeting these molecules could be used to more finely control T cell trafficking in the treatment of inflammatory diseases and for the design of next-generation adoptive T cell therapies."
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27509
DOI - https://doi.org/10.18632/oncotarget.27509
Full text - https://www.oncotarget.com/article/27509/text/
Correspondence to - Mobin Karimi - karimim@upstate.edu
Keywords - graft-versus-host disease, CrkL, T cell, migration, inflammation
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Copyright © 2021 Impact Journals, LLC Impact Journals is a registered trademark of Impact Journals, LLC
Volume 11, Number 21 of Oncotarget reported that eligible patients with stable or responding mPDA after 6 months on chemotherapy were randomized 1:1 to metformin alone or with rapamycin, stratified by prior treatment with FOLFIRINOX. Metformin +/ rapamycin maintenance for mPDA was well-tolerated and several patients achieved stable disease associated with exceptionally long survival.
Dr. Dung T. Le from The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, 21287 said, "Pancreatic ductal adenocarcinoma (PDA) is aggressive cancer with high mortality at all stages and limited treatment options in the advanced setting."
Metformin is an antidiabetic drug in the biguanide class of agents which inhibits mTOR complex 1 primarily through AMP-kinase activation.
A synergistic effect of the combination of metformin with rapamycin was suggested by preclinical studies demonstrating enhanced inhibition of mTOR in a pancreatic cancer cell line and better growth inhibition of pancreatic cancer cells in a xenograft tumor model with the combination than either agent alone.
Based on this, they conducted an exploratory study of metformin with or without rapamycin in patients with mPDA in the maintenance setting.
The Le Research Team concluded in their Oncotarget Research Article, "the administration of metformin with or without rapamycin in patients with mPDA who achieve a response to chemotherapy is well-tolerated and was associated with better than expected overall survival in this study. Additional studies are needed to prospectively evaluate the role of these agents compared to a maintenance chemotherapy or observation only approach."
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27586
DOI - https://doi.org/10.18632/oncotarget.27586
Full text - https://www.oncotarget.com/article/27586/text/
Correspondence to - Dung T. Le - dle@jhmi.edu
Keywords - pancreatic cancer, mTOR inhibition, maintenance therapy, metformin
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Copyright © 2021 Impact Journals, LLC Impact Journals is a registered trademark of Impact Journals, LLC
Oncotarget published "Innovating and expanding weight loss strategies for breast cancer survivors" which reported that overweight and obesity are prevalent in over two thirds of the general population in the United States and are associated with an increased risk of malignancies, including breast cancer.
This weight gain may increase risk of recurrence by 40–50%, and breast cancer-related mortality by 53–60% . Obesity at and following a breast cancer diagnosis is associated with poor quality of life and increased risk of adverse treatment effects.
Dr. Jennifer Y. Sheng from The Johns Hopkins Sidney Kimmel Comprehensive Cancer Center said, "...survivorship guidelines recommend that weight loss should be a priority for overweight/obese survivors."
Numerous clinical trials have tested behavioral strategies for weight loss in survivors of early stage breast cancer, including modifications in diet, remote or group interventions. These authors evaluated several outcomes including: whether a 12-month remotely delivered behavioral weight loss intervention allows a greater proportion of breast cancer survivors to achieve 5% weight compared to a self-directed approach, modulation of biomarkers of cancer risk including metabolism, inflammation, and telomere length, and changes in patient-reported outcomes.
While levels of inflammatory cytokines improved, changes were not statistically significant. However, studies show that weight loss of 10% has been associated with modulation of serum and tissue biomarkers, such as Ki-67, adiponectin, adiponectin to leptin ratio, sex hormone binding globulin, estradiol, testosterone and insulin.
The Sheng Research Team concluded in their Oncotarget Research Output that as there may be barriers to in-person or group interventions and studies aim for scalability, we can expect remote interventions like POWER-remote to be used as a practical strategy for weight loss.
Remote strategies that incorporate a comprehensive assessment and coaching are necessary to ensure safe and cost effective treatment for cancer survivors struggling with weight loss.
Sign up for free Altmetric alerts about this article - Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27898
DOI - https://doi.org/10.18632/oncotarget.27898
Correspondence to - Jennifer Y. Sheng - jsheng7@jhmi.edu
Keywords - breast cancer, obesity, lifestyle interventions
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Copyright © 2021 Impact Journals, LLC Impact Journals is a registered trademark of Impact Journals, LLC
Oncotarget published "Innovating and expanding weight loss strategies for breast cancer survivors" which reported that overweight and obesity are prevalent in over two thirds of the general population in the United States and are associated with an increased risk of malignancies, including breast cancer.
This weight gain may increase risk of recurrence by 40–50%, and breast cancer-related mortality by 53–60% . Obesity at and following a breast cancer diagnosis is associated with poor quality of life and increased risk of adverse treatment effects.
Dr. Jennifer Y. Sheng from The Johns Hopkins Sidney Kimmel Comprehensive Cancer Center said, "...survivorship guidelines recommend that weight loss should be a priority for overweight/obese survivors."
Numerous clinical trials have tested behavioral strategies for weight loss in survivors of early stage breast cancer, including modifications in diet, remote or group interventions. These authors evaluated several outcomes including: whether a 12-month remotely delivered behavioral weight loss intervention allows a greater proportion of breast cancer survivors to achieve 5% weight compared to a self-directed approach, modulation of biomarkers of cancer risk including metabolism, inflammation, and telomere length, and changes in patient-reported outcomes.
While levels of inflammatory cytokines improved, changes were not statistically significant. However, studies show that weight loss of 10% has been associated with modulation of serum and tissue biomarkers, such as Ki-67, adiponectin, adiponectin to leptin ratio, sex hormone binding globulin, estradiol, testosterone and insulin.
The Sheng Research Team concluded in their Oncotarget Research Output that as there may be barriers to in-person or group interventions and studies aim for scalability, we can expect remote interventions like POWER-remote to be used as a practical strategy for weight loss.
Remote strategies that incorporate a comprehensive assessment and coaching are necessary to ensure safe and cost effective treatment for cancer survivors struggling with weight loss.
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27898
DOI - https://doi.org/10.18632/oncotarget.27898
Correspondence to - Jennifer Y. Sheng - jsheng7@jhmi.edu
Keywords - breast cancer, obesity, lifestyle interventions
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget published "Reversing oncogenic transformation with iron chelation" which reported that cancer cells accumulate iron to supplement their aberrant growth and metabolism.
Depleting cells of iron by iron chelators has been shown to be selectively cytotoxic to cancer cells in vitro and in vivo. A plethora of studies have shown iron chelators can reverse some of the major hallmarks and enabling characteristics of cancer. Iron chelators inhibit signalling pathways that drive proliferation, migration and metastasis as well as return tumour suppressive signalling. Iron chelators target cancer cell metabolism, attenuating oxidative phosphorylation and glycolysis.
Dr. Gina Abdelaal from The Northumbria University said, "Iron is vital for normal cell growth and survival."
Cancer is an evolutionary maverick, which exploits its trademark genomic instability to drain environmental resources. As an enzyme cofactor, iron is responsible for many cellular processes including mitochondrial metabolism and DNA synthesis. As iron can drive cellular proliferation, cancer cells have an adapted iron metabolism allowing increased iron accumulation. The thiosemicarbazone class is a later stage of iron chelator evolution which manifested in 1992.
Unlike their predecessor DFO, thiosemicarbazone chelators are capable of inducing reactive oxygen species. Triapine is a thiosemicarbazone; its primary mode of action is thought to be ribonucleotide reductase inhibition with a higher potency than commonly used ribonucleotide reductase inhibitor, hydroxyurea. This approach is predicted to protect healthy tissues from the cytotoxic effects as the timing and place of the drug release can be controlled.
Encapsulating Dp44mT in PLGA nanoparticles enhanced its ability to induce apoptosis and improved its selectivity towards cancer cells.
At present many more classes of iron chelators are being taken into consideration as potential cancer therapy candidates.
The Abdelaal Research Team concluded in their Oncotarget Research Output that based on the data presented in this review iron chelators could potentially reverse many of the key hallmarks of cancer. Stripping the cells of iron impacts many cellular targets with some targets still undiscovered. NDRG1 has been proven to be the common link between the ability of iron chelators to reverse many of the hallmarks of cancer as overexpression of NDRG1 mimics the impact of iron chelation on several signalling pathways. There are still many unanswered questions about the mechanism of action of iron chelators.
A consensus must be reached on the impact of iron chelation on angiogenesis through in vivo studies. As STAT3 is essential for VEGF gene expression and iron chelation attenuates STAT3 dimerisation and nuclear localisation. The cleaved isoform is only present in cancer cells and could potentially be oncogenic. Although many mechanistic studies have been undertaken iron chelators, the complexity of cell signalling remains a hurdle preventing the discovery of all cellular targets of iron chelation. A potential way of discovering new targets is combining iron chelators with well-characterised cancer therapeutics.
DOI - https://doi.org/10.18632/oncotarget.27866
Full text - https://www.oncotarget.com/article/27866/text/
Correspondence to - Gina Abdelaal - gina.abdelaal@northumbria.ac.uk
Keywords - iron chelator, oncogenesis, selective cytotoxicity, hallmarks of cancer, NDRG1
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget published "Reversing oncogenic transformation with iron chelation" which reported that cancer cells accumulate iron to supplement their aberrant growth and metabolism.
Depleting cells of iron by iron chelators has been shown to be selectively cytotoxic to cancer cells in vitro and in vivo. A plethora of studies have shown iron chelators can reverse some of the major hallmarks and enabling characteristics of cancer. Iron chelators inhibit signalling pathways that drive proliferation, migration and metastasis as well as return tumour suppressive signalling. Iron chelators target cancer cell metabolism, attenuating oxidative phosphorylation and glycolysis.
Dr. Gina Abdelaal from The Northumbria University said, "Iron is vital for normal cell growth and survival."
Cancer is an evolutionary maverick, which exploits its trademark genomic instability to drain environmental resources. As an enzyme cofactor, iron is responsible for many cellular processes including mitochondrial metabolism and DNA synthesis. As iron can drive cellular proliferation, cancer cells have an adapted iron metabolism allowing increased iron accumulation. The thiosemicarbazone class is a later stage of iron chelator evolution which manifested in 1992.
Unlike their predecessor DFO, thiosemicarbazone chelators are capable of inducing reactive oxygen species. Triapine is a thiosemicarbazone; its primary mode of action is thought to be ribonucleotide reductase inhibition with a higher potency than commonly used ribonucleotide reductase inhibitor, hydroxyurea. This approach is predicted to protect healthy tissues from the cytotoxic effects as the timing and place of the drug release can be controlled.
Encapsulating Dp44mT in PLGA nanoparticles enhanced its ability to induce apoptosis and improved its selectivity towards cancer cells.
At present many more classes of iron chelators are being taken into consideration as potential cancer therapy candidates.
The Abdelaal Research Team concluded in their Oncotarget Research Output that based on the data presented in this review iron chelators could potentially reverse many of the key hallmarks of cancer. Stripping the cells of iron impacts many cellular targets with some targets still undiscovered. NDRG1 has been proven to be the common link between the ability of iron chelators to reverse many of the hallmarks of cancer as overexpression of NDRG1 mimics the impact of iron chelation on several signalling pathways. There are still many unanswered questions about the mechanism of action of iron chelators.
A consensus must be reached on the impact of iron chelation on angiogenesis through in vivo studies. As STAT3 is essential for VEGF gene expression and iron chelation attenuates STAT3 dimerisation and nuclear localisation. The cleaved isoform is only present in cancer cells and could potentially be oncogenic. Although many mechanistic studies have been undertaken iron chelators, the complexity of cell signalling remains a hurdle preventing the discovery of all cellular targets of iron chelation. A potential way of discovering new targets is combining iron chelators with well-characterised cancer therapeutics.
DOI - https://doi.org/10.18632/oncotarget.27866
Full text - https://www.oncotarget.com/article/27866/text/
Correspondence to - Gina Abdelaal - gina.abdelaal@northumbria.ac.uk
Keywords - iron chelator, oncogenesis, selective cytotoxicity, hallmarks of cancer, NDRG1
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
The cover for issue 36 of Oncotarget features Figure 7, "Knockdown of APOBEC3B is associated with a lower tumor growth in an adrenocortical carcinoma xenograft mouse model," by Gara, et al. which reported that the role of APOBEC3B in adrenocortical carcinoma and the mechanisms through which its expression is regulated in cancer are not fully understood.
Here, the authors report that APOBEC3B is overexpressed in ACC and it regulates cell proliferation by inducing S phase arrest. They show high APOBEC3B expression is associated with a higher copy number gain/loss at chromosome 4 and 8 and TP53 mutation rate in ACC.
GATA3 was identified as a positive regulator of APOBEC3B expression and directly binds the APOBEC3B promoter region.
Both GATA3 and APOBEC3B expression levels were associated with patient survival.
This Oncotarget study provides novel insights into the function and regulation of APOBEC3B expression in addition to its known mutagenic ability.
Dr. Electron Kebebew from Stanford University said, "Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy."
The distinct pattern of DNA base alterations has been characterized in the cancer genome using high throughput deep sequencing technologies, that reflect the underlying mutational process.
Whole-genome and exome mutation analysis of The Cancer Genome Atlas data on multiple cancers has revealed that this pattern is consistent with the deaminase activity of the AID/APOBEC family of enzymes, therefore, implying its significance as an endogenous mutator and a crucial contributor to somatic mutations and genomic instability.
APOBEC3B is overexpressed in ovarian cancer cell lines and high-grade primary ovarian cancers.
In addition, APOBEC3B expression is positively correlated with the total mutation load, as well as, elevated levels of transversion mutations.
Given there are no well-established exogenous factors associated with ACC, the Oncotarget authors postulated whether APOBEC3B could be an endogenous mechanism of genomic instability/mutations in ACC and investigated its function in vitro and in vivo.
The Kebebew Research Team concluded in their Oncotarget Research Paper, "APOBEC3B overexpressed in ACC, and is associated with DNA damage, S phase arrest, higher copy number alterations and TP53 mutations in ACC. For the first time, we demonstrated that GATA3 directly regulates the expression of APOBEC3B and that both are prognostic markers in ACC."
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27703
Full text - https://www.oncotarget.com/article/27703/text/
Correspondence to - Electron Kebebew - kebebew@stanford.edu
Keywords - adrenocortical carcinoma, APOBEC3B, GATA3, prognosis, DNA damage
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Copyright © 2021 Impact Journals, LLC Impact Journals is a registered trademark of Impact Journals, LLC
The cover for issue 36 of Oncotarget features Figure 7, "Knockdown of APOBEC3B is associated with a lower tumor growth in an adrenocortical carcinoma xenograft mouse model," by Gara, et al. which reported that the role of APOBEC3B in adrenocortical carcinoma and the mechanisms through which its expression is regulated in cancer are not fully understood.
Here, the authors report that APOBEC3B is overexpressed in ACC and it regulates cell proliferation by inducing S phase arrest. They show high APOBEC3B expression is associated with a higher copy number gain/loss at chromosome 4 and 8 and TP53 mutation rate in ACC.
GATA3 was identified as a positive regulator of APOBEC3B expression and directly binds the APOBEC3B promoter region.
Both GATA3 and APOBEC3B expression levels were associated with patient survival.
This Oncotarget study provides novel insights into the function and regulation of APOBEC3B expression in addition to its known mutagenic ability.
Dr. Electron Kebebew from Stanford University said, "Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy."
The distinct pattern of DNA base alterations has been characterized in the cancer genome using high throughput deep sequencing technologies, that reflect the underlying mutational process.
Whole-genome and exome mutation analysis of The Cancer Genome Atlas data on multiple cancers has revealed that this pattern is consistent with the deaminase activity of the AID/APOBEC family of enzymes, therefore, implying its significance as an endogenous mutator and a crucial contributor to somatic mutations and genomic instability.
APOBEC3B is overexpressed in ovarian cancer cell lines and high-grade primary ovarian cancers.
In addition, APOBEC3B expression is positively correlated with the total mutation load, as well as, elevated levels of transversion mutations.
Given there are no well-established exogenous factors associated with ACC, the Oncotarget authors postulated whether APOBEC3B could be an endogenous mechanism of genomic instability/mutations in ACC and investigated its function in vitro and in vivo.
The Kebebew Research Team concluded in their Oncotarget Research Paper, "APOBEC3B overexpressed in ACC, and is associated with DNA damage, S phase arrest, higher copy number alterations and TP53 mutations in ACC. For the first time, we demonstrated that GATA3 directly regulates the expression of APOBEC3B and that both are prognostic markers in ACC."
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27703
Full text - https://www.oncotarget.com/article/27703/text/
Correspondence to - Electron Kebebew - kebebew@stanford.edu
Keywords - adrenocortical carcinoma, APOBEC3B, GATA3, prognosis, DNA damage
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Copyright © 2021 Impact Journals, LLC Impact Journals is a registered trademark of Impact Journals, LLC
According to the Centers for Disease Control and Prevention (CDC), colorectal cancer is the second leading cause of cancer death in the United States. Researchers have observed elevated levels of the macrophage inflammatory protein CCL20 in colorectal cancer. Interactions between CCL20 and its receptor, CCR6, promote colorectal cancer through effects on neoplastic epithelial cells and modulation of the tumor microenvironment. However, the mechanism of these effects are not yet fully understood.
“In particular, CCL20 acting on CCR6 expressed by colorectal cancer neoplastic epithelial cells induces proliferation, migration, and initiates an auto-feedback loop by inducing further secretion of CCL20. The mechanisms through which CCL20-CCR6 interactions elicit these effects is poorly understood.”
Researchers—from the VA Boston Healthcare System, Harvard Medical School, Beth Israel Deaconess Medical Center, Dana-Farber Cancer Institute, and Brigham and Women’s Hospital—conducted a study investigating the signaling pathways and mechanisms that underlie this colorectal cancer-promoting molecule. In 2021, the team authored a research paper, which was chosen as the cover paper of Oncotarget’s Volume 12, Issue 24, and entitled, “CCL20 induces colorectal cancer neoplastic epithelial cell proliferation, migration, and further CCL20 production through autocrine HGF-c-Met and MSP-MSPR signaling pathways."
Full blog - https://www.oncotarget.org/2021/11/24/new-study-investigation-of-colorectal-cancer-promoting-protein/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28131
DOI - https://doi.org/10.18632/oncotarget.28131
Full text - https://www.oncotarget.com/article/28131/text/
Correspondence to - Jason S. Gold - jgold@bwh.harvard.edu
Keywords - CCL20, CCR6, HGF, MSP, colorectal cancer
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to short summaries of the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 24. https://www.oncotarget.com/archive/v12/i24/
Research Paper (Cover) - “CCL20 induces colorectal cancer neoplastic epithelial cell proliferation, migration, and further CCL20 production through autocrine HGF-c-Met and MSP-MSPR signaling pathways” https://doi.org/10.18632/oncotarget.28131
Research Paper - “The potential of PIVKA-II as a treatment response biomarker in hepatocellular carcinoma: a prospective United Kingdom cohort study” https://doi.org/10.18632/oncotarget.28136
Research Paper - “Caloric restriction causes a distinct reorganization of the lipidome in quiescent and non-quiescent cells of budding yeast” https://doi.org/10.18632/oncotarget.28133
Research Paper - “Optimization of tumor spheroid model in mesothelioma and lung cancers and anti-cancer drug testing in H2052/484 spheroids” https://doi.org/10.18632/oncotarget.28134
Research Paper - “Circulating low density neutrophils of breast cancer patients are associated with their worse prognosis due to the impairment of T cell responses” https://doi.org/10.18632/oncotarget.28135
Research Paper - “Regional and temporal heterogeneity of epithelial ovarian cancer tumor biopsies: implications for therapeutic strategies” https://doi.org/10.18632/oncotarget.10505
Editorial - “Undetected Barrett’s esophagus: how do we improve early detection?” https://doi.org/10.18632/oncotarget.28005 (PDF Download)
Research Perspective - “Hepatitis B x antigen (HBx) is an important therapeutic target in the pathogenesis of hepatocellular carcinoma” https://doi.org/10.18632/oncotarget.28077
Keywords - CCL20, colorectal cancer, hepatocellular carcinoma, biomarker, cellular aging, cellular quiescence, cancer patient, lung tumor, breast cancer, ovarian cancer, Barrett's esophagus, chronic liver disease, cancer, science, research, oncology
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget
Oncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oxybenzone (benzophenone-3; BP-3) is a toxic endocrine-disrupting chemical (EDC). Alarmingly, this chemical has been identified as a common ingredient in some brands of sunscreen. Oxybenzone can often be found in humans, household dust, fish and, due to its widespread human use, the water environment—causing harm to coral reefs and other murine life. Previous studies have shown that environmental toxins and estrogenic chemicals have emerged as potential culprits in the promotion of breast cancer. Furthermore, oxybenzone has been known to have estrogenic and anti-estrogenic properties.
“Although BP-3 has a very short half-life, its presence is widespread in human urine [9], in as much as 98% of the general U.S. population [13].”
Researchers from the Breast Cancer and the Environment Research Program at Michigan State University studied the diet-dependent effects of oxybenzone in mouse models of mammary tumorigenesis during puberty and adulthood. Their paper was published by Oncotarget in 2020, and entitled, “Benzophenone-3 promotion of mammary tumorigenesis is diet-dependent.”
“We [previously] demonstrated enhancement of mammary tumorigenesis by a diet high in saturated animal fat (HFD) [5–8]. Thus, examination of the activity of EDCs in a dietary context may provide additional insight into the potential role of EDCs in promoting breast cancer.”
Full blog - https://www.oncotarget.org/2021/11/17/sunscreen-ingredient-promotes-breast-cancer-in-diet-dependent-manner/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27831
DOI - https://doi.org/10.18632/oncotarget.27831
Full text - https://www.oncotarget.com/article/27831/text/
Correspondence to - Richard C. Schwartz - schwart9@msu.edu and Sandra Z. Haslam - shaslam@msu.edu
Keywords - oxybenzone, benzophenone-3, mammary tumorigenesis, dietary animal fat, breast cancer
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget Volume 11, Issue 8 reported Independent validation cohorts of 599 cases of early-stage CRC and 91 cases of late-stage CRC were examined.
Multivariate and univariate survival analyses revealed that high expression of P4HA1 protein was an independent poor prognostic marker for patients with early-stage CRC, especially of the microsatellite stable subtype.
Dr. Michael H. Roehrl from the Department of Pathology, Memorial Sloan Kettering Cancer Center as well as the Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center said, "Colorectal cancer (CRC) is one of the most prevalent malignant tumors and the third leading cause of cancer deaths worldwide."
However, molecular biomarkers with more precise prognostic value, preferably with an underlying functional pathophysiologic rationale, are needed, as such markers would enable the scientists to better stratify risk of recurrence in resected early-stage CRC after resection and more accurately select patients for adjuvant therapy, while avoiding overtreatment in low-risk early-stage CRC.
Proteomics with latest-generation liquid chromatography-mass spectrometry can detect 5,000 - 10,000 proteins in one shotgun sequencing event, and such powerful and sensitive technology may enable the researchers to discover prognostic protein biomarkers for early-stage CRC that previous genomic and transcriptomic analyses would have missed.
Combining results from 712 patients, their study shows that collagen prolyl 4-hydroxylase alpha 1 protein expression robustly risk-stratifies early-stage CRC.
The discovery of P4HA1 outcome stratification in early-stage CRC and, in particular, its MSS subtype, may provide an avenue for early-stage CRC risk prognosis and thus improve cancer treatment outcomes by tailoring follow-up frequency and adjuvant therapy intensity.
The Roehrl Research Team concluded, in their Oncotarget Research Paper, that early-stage CRC presents frequent challenges in clinical patient management in that it is currently impossible to predict which patients will have aggressive disease and thus benefit the most from intensive adjuvant chemotherapy vs. those patients who will have less aggressive disease and benefit from surgery alone.
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27491
Full text - https://www.oncotarget.com/article/27491/text/
Correspondence to - Michael H. Roehrl - roehrlm@mskcc.org
Keywords - P4HA1, colorectal cancer, biomarker, prognosis, pathology
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.impactjournals.com/ or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Copyright © 2021 Impact Journals, LLC Impact Journals is a registered trademark of Impact Journals, LLC
Oncotarget Volume 11, Issue 8 reported Independent validation cohorts of 599 cases of early-stage CRC and 91 cases of late-stage CRC were examined.
Multivariate and univariate survival analyses revealed that high expression of P4HA1 protein was an independent poor prognostic marker for patients with early-stage CRC, especially of the microsatellite stable subtype.
Dr. Michael H. Roehrl from the Department of Pathology, Memorial Sloan Kettering Cancer Center as well as the Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center said, "Colorectal cancer (CRC) is one of the most prevalent malignant tumors and the third leading cause of cancer deaths worldwide."
However, molecular biomarkers with more precise prognostic value, preferably with an underlying functional pathophysiologic rationale, are needed, as such markers would enable the scientists to better stratify risk of recurrence in resected early-stage CRC after resection and more accurately select patients for adjuvant therapy, while avoiding overtreatment in low-risk early-stage CRC.
Proteomics with latest-generation liquid chromatography-mass spectrometry can detect 5,000 - 10,000 proteins in one shotgun sequencing event, and such powerful and sensitive technology may enable the researchers to discover prognostic protein biomarkers for early-stage CRC that previous genomic and transcriptomic analyses would have missed.
Combining results from 712 patients, their study shows that collagen prolyl 4-hydroxylase alpha 1 protein expression robustly risk-stratifies early-stage CRC.
The discovery of P4HA1 outcome stratification in early-stage CRC and, in particular, its MSS subtype, may provide an avenue for early-stage CRC risk prognosis and thus improve cancer treatment outcomes by tailoring follow-up frequency and adjuvant therapy intensity.
The Roehrl Research Team concluded, in their Oncotarget Research Paper, that early-stage CRC presents frequent challenges in clinical patient management in that it is currently impossible to predict which patients will have aggressive disease and thus benefit the most from intensive adjuvant chemotherapy vs. those patients who will have less aggressive disease and benefit from surgery alone.
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27491
Full text - https://www.oncotarget.com/article/27491/text/
Correspondence to - Michael H. Roehrl - roehrlm@mskcc.org
Keywords - P4HA1, colorectal cancer, biomarker, prognosis, pathology
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.impactjournals.com/ or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Copyright © 2021 Impact Journals, LLC Impact Journals is a registered trademark of Impact Journals, LLC
Here the research team tested a safe and well-established microbe-based immune adjuvant to restore immune homeostasis and counteract inflammation-associated obesity in animal models.
Taken together, they concluded that oral vaccination with cholera toxin B helps stimulate health-protective immune responses that counteract age-associated obesity.
Dr. Susan E. Erdman from the Division of Comparative Medicine, at the Massachusetts Institute of Technology in Cambridge, MA, United States said, "The global burden of chronic inflammatory diseases is increasing at alarming rates."
The continuous rise of obesity, cardiovascular and chronic respiratory diseases, diabetes, infertility, allergy and autoimmunity, cancer, and central nervous system dysfunctions, including anxiety and autism, appears to link with modernized lifestyle but remains inexplicable.
Underlying systemic immune imbalances linked with bacteria residing in the gut have been proposed as a probable cause of obesity.
In this context, obesity is one of many chronic inflammatory diseases associated with modern living.
Important effects of gut microbiota in mammalian physiology, including metabolism and CNS functions, place gut microbe-immune cell interactions in the hypothetical center of chronic inflammatory disorders such as obesity.
In this regard, postbiotic gut bacterial fractions used for oral immunizations have been found to stabilize the immune system and counteract destructive inflammatory responses later in life in both humans and animals.
Immune adjuvant properties of cholera-toxin, make it an attractive tool for induction of tolerance that stabilizes the immune system.
The Erdman research team concluded, "Indeed, systemic immune imbalances related to failure of tolerance have been proposed as a cause of extra-intestinal cancer linked with bacteria residing in the gut.
It remains to be seen whether this gut immune-centric strategy broadly translates to successes in the clinic; however, the versatility of ct B to manipulate immune responses make this protein a promising adjuvant for vaccine development to combat a growing Westernized public health crisis."
Full text - https://www.oncotarget.com/article/27137/text/
Correspondence to - Susan E. Erdman - serdman@mit.edu
Keywords - body weight, mouse, exotoxin subunit B, CLS, inflammation
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with @Oncotarget
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM
Copyright © 2021 Impact Journals, LLC Impact Journals is a registered trademark of Impact Journals, LLC
The identification of an actionable gene mutation or translocation in patients with cancer can give researchers a target for new drug therapies. One such mutation, found in some patients with non-small cell lung cancer (NSCLC), is anaplastic lymphoma kinase (ALK) gene rearrangement. However, the exact population of patients that present with ALK rearrangement has not been fully characterized. Identifying the subpopulation of patients who present with ALK rearrangement may lead to better overall treatment outcomes.
Researchers—from University of Mississippi Medical Center, Roche Information Solutions, Roche Diagnostics Corporation, Genesis Research, and Houston Methodist Hospital—conducted a retrospective study of nearly 20,000 patients with advanced NSCLC (aNSCLC). The researchers assessed ALK rearrangement prevalence in the cohort overall and then categorized the data using patient characteristics. Their paper was published on the cover of Oncotarget’s Volume 12, Issue 23, and entitled, “Anaplastic lymphoma kinase rearrangement prevalence in patients with advanced non-small cell lung cancer in the United States – retrospective real world data”.
“We performed a retrospective study of a database to acquire real-world clinical data on the frequency of the translocation in a large pool of patients drawn primarily from community hospitals and practices.”
Full blog - https://www.oncotarget.org/2021/11/10/new-study-alk-rearrangement-among-lung-cancer-patients/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28114
DOI - https://doi.org/10.18632/oncotarget.28114
Full text - https://www.oncotarget.com/article/28114/text/
Correspondence to - Eric H. Bernicker - bernicker@houstonmethodist.org
Keywords - ALK rearrangement, NSCLC, prevalence
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 23. https://www.oncotarget.com/archive/v12/i23/
Research Paper (Cover) - “Anaplastic lymphoma kinase rearrangement prevalence in patients with advanced non-small cell lung cancer in the United States – retrospective real world data” https://doi.org/10.18632/oncotarget.28114
News - “Excitement for our future” https://doi.org/10.18632/oncotarget.28116 (PDF Download)
Editorial - “Interferon-γ/IRF-1 pathway regulatory mechanisms of PD-L1 expression and relevance for immune checkpoint blockade in hepatocellular carcinoma (HCC)” https://doi.org/10.18632/oncotarget.27995 (PDF Download)
Editorial - “Results from a randomized trial combining trastuzumab with a peptide vaccine suggest a role for HER2-targeted therapy in triple-negative breast cancer” https://doi.org/10.18632/oncotarget.27998 (PDF Download)
Keywords - ALK rearrangement, non-small cell lung cancer (NSCLC), prevalence, multi-omics, molecular signatures, BRCA, HER2, triple negative breast cancer, breast cancer, hepatocellular carcinoma, cancer, science, research, oncology
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget
Oncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Over the past few decades, numerous studies have emerged using the promising strategy of bacteria as vehicles to deliver drugs or genes in tumor‐targeted therapies. Researchers say that bacterial cancer therapy may be able to overcome some of the limitations that conventional cancer therapy is stunted by, including the development of drug resistance.
In a 2020 study, researchers—from Yale University, the University of Missouri, Harry S. Truman Memorial Veterans Hospital, Cancer Research Center in Missouri, and DeSales University—investigated a tumor-targeting Salmonella typhimurium strain of bacteria (CRC2631) in prostate cancer-positive mouse-models and evaluated its toxicity, targeting ability and genetic stability. Their trending paper was published by Oncotarget and entitled, “Evaluations of CRC2631 toxicity, tumor colonization, and genetic stability in the TRAMP prostate cancer model.”
“Here, we report the toxicological and in vivo tumor-targeting profiles of CRC2631 in the syngeneic and autochthonous mouse model of aggressive prostate cancer, TRAMP (Transgenic Adenocarcinoma of Mouse Prostate).”
Full blog - https://www.oncotarget.org/2021/01/21/bacterial-therapy-experiments-in-prostate-cancer/
Press release - https://www.oncotarget.com/news/pr/evaluations-in-the-tramp-prostate-cancer-model/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27769
DOI - https://doi.org/10.18632/oncotarget.27769
Full text - https://www.oncotarget.com/article/27769/text/
Correspondence to - Yves C. Chabu - chabuc@missouri.edu
Keywords - salmonella, cancer targeting, prostate cancer, immunotherapy, TRAMP
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget published "Benzophenone-3 promotion of mammary tumorigenesis is diet-dependent" which reported that Benzophenone-3 is a putative endocrine disrupting chemical and common ingredient in sunscreens.
Although benzophenone-3 seemed protective on low-fat diet, spindle cell tumors arising in these mice showed increased proliferation and decreased apoptosis. This points to a need for further studies of benzophenone-3 in both animal models and humans as a potential breast cancer risk factor, as well as a more general need to evaluate endocrine disrupting chemicals in varying dietary contexts.
Dr. Richard C. Schwartz and Dr. Sandra Z. Haslam, both from The Michigan State University said, "Ovarian hormones are strongly implicated in the etiology of breast cancer."
Putative endocrine disrupting chemicals, particularly estrogenic chemicals, have emerged as suspects in environmental promotion of breast cancer. Environmental EDCs have the potential to act as agonists or antagonists in critical hormonally regulated processes, such as mammary gland development and mammary tumorigenesis - this warrants evaluation of their potential in promoting breast cancer.
More recently, BP-3 was demonstrated to have pathological effects on coral. Although BP-3 has a very short half-life, its presence is widespread in human urine, in as much as 98% of the general U.S. population.
A recent preliminary study found plasma concentrations greater than 0.5 ng/mL among a small human cohort using heavy topical applications of commercial sunscreens. The present study examined the interaction of BP-3 with HFD on mammary tumorigenesis in BALB/c mice, using the Trp53-null transplantation model. A level of BP-3 exposure was used that yielded levels in murine urine similar to that observed in humans subjected to heavy topical exposure of BP-3-containing commercial sunscreen. These authors found that BP-3 had complex effects that were dependent upon dietary regimen and tumor histopathology.
The Schwartz/Haslam Research Team concluded in their Oncotarget Research Output that unlike several earlier studies that found rather minimal BP-3 activity in vivo in rodents with doses higher than those in the current study: 1500 mg/kg BW/d; 1000 mg/kg BW/d; 150 mg/kg BW/d, these authors tumorigenesis experiments showed significant effects at 70 mg/kg BW/d. This dosage elicits levels of BP-3 excretion in urine similar to that observed in humans with heavy topical application of BP-3-containing sunscreen. Furthermore, their initial experiments in wild type BALB/c mice found significant effects on mammary epithelial proliferation at only 7 mg/kg BW/d. These observations suggest caution in the use of BP-3-containing sunscreens.
DOI - https://doi.org/10.18632/oncotarget.27831
Full text - https://www.oncotarget.com/article/27831/text/
Correspondence to - Richard C. Schwartz - schwart9@msu.edu and Sandra Z. Haslam - shaslam@msu.edu
Keywords - oxybenzone, benzophenone-3, mammary tumorigenesis, dietary animal fat, breast cancer
About Oncotarget
Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Copyright © 2021 Impact Journals, LLC Impact Journals is a registered trademark of Impact Journals, LLC
The most common type of breast cancer in the United States is HR+/HER2− breast cancer. Patients with HR+/HER2− breast cancer often face the threat of distant recurrence—long after the completion of their treatment. Previous studies have found that high levels of tumor infiltrating lymphocytes (TILs) were associated with improved outcomes and recurrence-free survival in patients with HR+/HER2− breast cancer. These studies, and many others, have prompted researchers to further develop and test cancer vaccines in an effort to elicit anti-tumor immune responses in these patients.
“Therefore, a rational combination therapy that enhances the immune-stimulatory properties of NAC [neoadjuvant chemotherapy], can provide long-term survival benefits for this patient population.”
Researchers from University of Arkansas for Medical Sciences, University of Texas Southwestern, Highlands Oncology Group, and Université Claude Bernard Lyon 1 conducted a new single-arm Phase Ib clinical trial. Early-stage HR+/HER2− breast cancer patients were treated with carbohydrate-mimetic peptides, the P10s-PADRE vaccine, in combination with chemotherapy treatments. Their paper was chosen as the cover of Oncotarget’s Volume 12, Issue 22, and entitled, “P10s-PADRE vaccine combined with neoadjuvant chemotherapy in ER-positive breast cancer patients induces humoral and cellular immune responses.”
“The main objective of our study was to determine an appropriate schedule to be used for adding the P10s-PADRE vaccine to cancer chemotherapy in the neoadjuvant setting considering the ability of the vaccine to elicit adequate antibody response.”
Full blog - https://www.oncotarget.org/2021/10/27/new-study-vaccine-enhances-breast-cancer-treatment/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28083
DOI - https://doi.org/10.18632/oncotarget.28083
Full text - https://www.oncotarget.com/article/28083/text/
Correspondence to - Behjatolah Monzavi-Karbassi - karbassi@uams.edu
Keywords - cancer vaccine, peptide mimotopes, combination therapy, breast cancer
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 22. https://www.oncotarget.com/archive/v12/i22/
Research Paper (Cover) - “P10s-PADRE vaccine combined with neoadjuvant chemotherapy in ER-positive breast cancer patients induces humoral and cellular immune responses” https://doi.org/10.18632/oncotarget.28083
Research Paper - “Dishevelled-1 DIX and PDZ domain lysine residues regulate oncogenic Wnt signaling” https://doi.org/10.18632/oncotarget.28089
Research Paper - “THSB2 as a prognostic biomarker for patients diagnosed with metastatic pancreatic ductal adenocarcinoma” https://doi.org/10.18632/oncotarget.28099
Research Paper - “Comparison of MET gene amplification analysis by next-generation sequencing and fluorescence in situ hybridization” https://doi.org/10.18632/oncotarget.28092
Review - “Emerging approaches of wound healing in experimental models of high-grade oral mucositis induced by anticancer therapy” https://doi.org/10.18632/oncotarget.28091
Editorial - “Future directions for immunotherapy in meningioma treatment” https://doi.org/10.18632/oncotarget.27994 (PDF Download)
Editorial - “Clinicopathological utility of human epidermal growth factor receptor 2 (HER2)-heterogeneity for next-generation treatments of triple-negative breast cancer” https://doi.org/10.18632/oncotarget.28007 (PDF Download)
Keywords - cancer vaccine, dishevelled (DVL), next-generation sequencing (NGS), oral mucositis, meningioma, immunotherapy, HER2 low, pancreatic cancer, breast cancer, non-small cell lung cancer (NSCLC), colorectal cancer, cancer, science, research, oncology
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget
Oncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Cancer cells have been known to use sagacious methods of evading apoptosis and mysteriously overcoming powerful anti-cancer therapies. One such method of evasion has recently been identified as the process of epithelial-mesenchymal transition (EMT) and its reverse process, mesenchymal-epithelial transition (MET). These transitions enable epithelial cells (structural/fixed) to gain mesenchymal cell (differentiating/mobile) functions, and vice versa. Researchers believe that epithelial-mesenchymal plasticity (EMP) allows cancers to become therapy resistant, determines cancer aggressiveness and allows metastatic cancer to mobilize and spread.
“Such dynamic and reversible switching can help tumor cells to overcome various challenges during disease progression such as anoikis, and assaults by the immune system.”
These processes and their characterization in cancer have been studied, however, questions remain about their molecular determinants and degree of reversibility, or irreversibility, in different cell populations and environments. To further elucidate EMT, researchers from Rice University, Northeastern University and the Indian Institute of Science used mechanistic mathematical models to identify possible mechanisms that may drive EMT response to an EMT-inducing signal in a given isogenic cell population. Their paper was published by Oncotarget in 2020, and entitled, “Epigenetic feedback and stochastic partitioning during cell division can drive resistance to EMT.”
Full blog - https://www.oncotarget.org/2021/10/21/emt-resistance-in-cancer-cells-and-two-potential-causes/
Press release - https://www.oncotarget.com/news/pr/epigenetic-feedback-and-stochastic-partitioning-can-drive-resistance-to-emt/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27651
DOI - https://doi.org/10.18632/oncotarget.27651
Full text - https://www.oncotarget.com/article/27651/text/
Correspondence to - Herbert Levine - h.levine@northeastern.edu and Mohit Kumar Jolly - mkjolly@iisc.ac.in
Keywords - epithelial-mesenchymal transition, mesenchymal-epithelial transition, GRHL2, epigenetics, asymmetric cell division
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Temozolomide (TMZ) is a powerful chemotherapeutic drug that is currently approved to treat brain cancer (glioblastoma, GBM) and advanced melanoma. TMZ has a remarkably precise molecular target—the O-6 position of guanine—and is capable of inducing DNA damage. This prodrug can elicit many responses in a variety of cancer cells, including cell death, autophagy and senescence. At present, there are over 300 clinical trials evaluating the efficacy of TMZ in combination with other agents in solid tumors. At least 25% of these trials include testing the efficacy of TMZ in breast, pancreatic, colorectal and lung cancers.
“Low MGMT levels in other types of cancer have resulted in the consideration of TMZ as a potential therapy beyond glioblastoma and melanoma.”
However, not all patients benefit from TMZ treatment, despite presenting with biomarkers known to predict TMZ treatment response, such as low O-6-Methylguanine-DNA methyltransferase (MGMTlow) and proficient DNA mismatch repair (MMRproficient). Researchers have found in some patients that the clinical efficacy of TMZ is hindered by inherent and acquired mechanisms of resistance.
In 2021, a team of researchers from Leidos Biomedical Research Inc. (the current operations and technical support contractor for the Frederick National Laboratory for Cancer Research) and the National Institutes of Health’s National Cancer Institute conducted a new study on TMZ. In an attempt to overcome TMZ resistance, they examined the in vitro and in vivo anti-tumor efficacy of TMZ when combined with ataxia telangiectasia and Rad3 related inhibitors (ATRi) and a wide variety of other inhibitor drugs. Their paper was published as the cover of Oncotarget’s Volume 12, Issue 21, and entitled, “ATR inhibition reverses the resistance of homologous recombination deficient MGMTlow/MMRproficient cancer cells to temozolomide.”
Full blog - https://www.impactjournals.com/journals/blog/oncotarget/new-study-atr-inhibition-reverses-chemo-resistance-in-subset-of-cells/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28090
DOI - https://doi.org/10.18632/oncotarget.28090
Full text - https://www.oncotarget.com/article/28090/text/
Correspondence to - Annamaria Rapisarda - rapisardaa@mail.nih.gov
Keywords - TMZ, MMR, ATR, HR, REV3L
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 21. https://www.oncotarget.com/archive/v12/i21/
Priority Research Paper (Cover) - “ATR inhibition reverses the resistance of homologous recombination deficient MGMTlow/MMRproficient cancer cells to temozolomide” https://doi.org/10.18632/oncotarget.28090
Research Paper - “Hyperprogression of a mismatch repair-deficient colon cancer in a humanized mouse model following administration of immune checkpoint inhibitor pembrolizumab” https://doi.org/10.18632/oncotarget.28086
Research Paper - “Luminescence complementation technology for the identification of MYC:TRRAP inhibitors” https://doi.org/10.18632/oncotarget.28078
Research Paper - “TAK1-inhibitors are cytotoxic for multiple myeloma cells alone and in combination with melphalan” https://doi.org/10.18632/oncotarget.28073
Research Paper - “The experiences and needs of Australian medical oncologists in integrating comprehensive genomic profiling into clinical care: a nation-wide survey” https://doi.org/10.18632/oncotarget.28076
Research Paper - “Low tumour-infiltrating lymphocyte density in primary and recurrent glioblastoma” https://doi.org/10.18632/oncotarget.28069
Research Paper - “Trends in oligomannosylation and α1,2-mannosidase expression in human cancers” https://doi.org/10.18632/oncotarget.28064
Research Paper - “TP53 mutations determined by targeted NGS in breast cancer: a case-control study” https://doi.org/10.18632/oncotarget.28071
Research Paper - “Association of four genetic variants with colorectal cancer in Kazakhstan population” https://doi.org/10.18632/oncotarget.28070
Editorial - “Javelin Head Neck 100: Should we combine immunotherapy with radiation therapy?” https://doi.org/10.18632/oncotarget.27987 (PDF Download)
Research Perspective - “Neddylation and anti-tumor immunity” https://doi.org/10.18632/oncotarget.28019
Keywords - ATR, cancer immunotherapy, drug discovery, comprehensive genomic profiling, glioblastoma, oligomannose, TP53 mutations, head and neck cancer, neddylation, breast cancer, colorectal cancer, multiple myeloma (MM), cancer, science, research, oncology
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget
Oncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Revelations in gene editing have made it possible to tinker in the vast human epigenome and to potentially alter the projection of diseases, including cancer. DNA methylation is an epigenetic mechanism that marks the regulation of gene expression. P53 is a highly-mutated gene in many patients with various cancerous tumors. The insulin-like growth factor binding protein 2 (IGFBP2) is an oncogene directly regulated through p53-mediated transcription. In tumorigenesis, this protein has both tumor-promoting and -suppressing functions.
“In this study, we will focus on the insulin-like growth factor binding protein 2 (IGFBP2), a recently discovered multitasked gene regulated by DNA methylation which has also been reported to function both as a tumor-promoting and -suppressing gene.”
Researchers from The Netherlands Cancer Institute in Amsterdam conducted a study using CRISPR/Cas9 technology and IGFBP2 to learn about the process of DNA methylation in various tumor settings. Their trending research paper was published in Oncotarget in 2021, and entitled, “Diverse transcriptional regulation and functional effects revealed by CRISPR/Cas9-directed epigenetic editing.”
“Here, we have taken advantage of CRISPR/dCas9 technology adapted for epigenetic editing through site-specific targeting of DNA methylation to characterize the transcriptional changes of the candidate gene and the functional effects on cell fate in different tumor settings.”
Full blog - https://www.impactjournals.com/journals/blog/oncotarget/exploration-of-gene-editing-in-the-tumor-setting/
Press release - https://www.oncotarget.com/news/pr/crispr-cas9-directed-epigenetic-editing/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28037
DOI - https://doi.org/10.18632/oncotarget.28037
Full text - https://www.oncotarget.com/article/28037/text/
Correspondence to - Miguel Vizoso - orcid.org/0000-0002-9992-2851 and Jacco van Rheenen - j.v.rheenen@nki.nl
Keywords - targeted DNA methylation, CRISPR/Cas9-based system, IGFBP2, epithelial-to-mesenchymal transition
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
The mammalian target of rapamycin (mTOR) operates within two distinct protein complexes—mTOR complex 1 (mTORC1) and complex 2 (mTORC2). These protein complexes are not yet fully understood, as they were only recently identified in humans in 1994. What researchers do know is that mTORC1 is involved in the regulation of many cellular processes and is a key mediator of cell growth and proliferation. mTORC1 is activated by growth factor receptor signals through the PI3K–AKT and RAS–ERK mitogen-activated protein kinase (MAPK) pathways.
The PI3K/AKT/mTOR pathway may be an efficacious target in the treatment of patients with non-small cell lung cancer (NSCLC). This theory is based on the identification of particular gene mutations in NSCLC that are associated with the PI3K/AKT/mTOR pathway. However, previous studies have not yet succeeded in defining an effective monotherapy or combination of therapies that targets this pathway while improving NSCLC patient outcome.
Researchers from Institut Curie, PSL University, Xentech, BioPôle Alfort, Hôpital Foch, and Centre Léon Bérard designed a study using a new methodology to test treatment combinations based on specific targets identified as biomarkers of resistance to PI3K-targeting treatments, and not based on the NSCLC mutations themselves. Their trending research paper was published by Oncotarget in 2021 and entitled, “High in vitro and in vivo synergistic activity between mTORC1 and PLK1 inhibition in adenocarcinoma NSCLC.”
Full blog - https://www.oncotarget.org/2021/09/30/trending-with-impact-unconventional-method-effectively-targets-nsclc/
Press release - https://www.oncotarget.com/news/pr/mtorc1-and-plk1-inhibition-in-adenocarcinoma-nsclc/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27930
DOI - https://doi.org/10.18632/oncotarget.27930
Full text - https://www.oncotarget.com/article/27930/text/
Correspondence to - Didier Decaudin - Didier.decaudin@curie.fr
Keywords - NSCLC, Pi3K signalling pathway, mTORC1, RAD001 (everolimus), PLK1
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
A small regulatory protein can be found not only in all humans, animals, plants and fungi, but in each and every eukaryotic cell. Following the discovery of these ubiquitous proteins in 1974, researchers aptly named them ubiquitin. Enzymes and/or ligases (enzymes that catalyze the formation of chemical bonds), allow ubiquitins to bind to substrate proteins. This process, known as ubiquitination, can initiate or prevent protein interactions, denote them for degradation and alter their activity and cellular location.
Aberrant ubiquitination may play an important role in tumorigenesis. At the core of solid tumors, hypoxia-inducible factor 1α (HIF-1α) is induced (by hypoxia) and allows cancer cells to adapt to the lack of oxygen. The accumulation of HIF-1α can also transcribe a number of genes well-known to be involved in cancer. Therefore, HIF-1α is an attractive, albeit difficult-to-pinpoint, therapeutic target in cancer. Researchers—from Brown University and Lifespan Cancer Institute—previously observed the stabilization of HIF-1α by the protein coding gene cyclin-dependent kinases CDK1. They further proposed that CDK4 may also be an HIF-1α stabilizer. However, the mechanism of HIF-1α’s regulation by CDK4 has yet to be fully elucidated.
“Till now, development of therapies targeting HIF-1α remains hindered. Therefore, it is imperative to explore the mechanism of HIF-1α regulation in cancer cells and investigate new possibilities to therapeutically target HIF-1 signaling.”
In 2021, the same team conducted a new study further investigating the molecular mechanisms of HIF-1α destabilization by CDK1 or CDK4/6 inhibitors in colorectal cancer. Their priority research paper was published as the cover of Oncotarget’s Volume 12, Issue 20, and entitled, “Identification of Smurf2 as a HIF-1α degrading E3 ubiquitin ligase.”
Full blog - https://www.oncotarget.org/2021/09/30/new-study-protein-analysis-reveals-novel-role-of-enzyme-in-cancer/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28081
DOI - https://doi.org/10.18632/oncotarget.28081
Full text - https://www.oncotarget.com/article/28081/text/
Correspondence to - Wafik S. El-Deiry - wafik@brown.edu
Keywords - Smurf2, CDK4/6 inhibition, HIF1alpha, hypoxia, cancer therapy
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to summaries of the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 20. https://www.oncotarget.com/archive/v12/i20/
Priority Research Paper (Cover) - “Identification of Smurf2 as a HIF-1α degrading E3 ubiquitin ligase” https://doi.org/10.18632/oncotarget.28081
Research Paper - “A high-throughput customized cytokinome screen of colon cancer cell responses to small-molecule oncology drugs” https://doi.org/10.18632/oncotarget.28079
Research Paper - “Opposing effects of BRCA1 mRNA expression on patient survival in breast and colorectal cancer and variations among African American, Asian, and younger patients” https://doi.org/10.18632/oncotarget.28082
Research Paper - “Pan-drug and drug-specific mechanisms of 5-FU, irinotecan (CPT-11), oxaliplatin, and cisplatin identified by comparison of transcriptomic and cytokine responses of colorectal cancer cells” https://doi.org/10.18632/oncotarget.28075
Research Paper - “Comparative microsomal proteomics of a model lung cancer cell line NCI-H23 reveals distinct differences between molecular profiles of 3D and 2D cultured cells” https://doi.org/10.18632/oncotarget.28072
Research Paper - “Tissue biodistribution and tumor targeting of near-infrared labelled anti-CD38 antibody-drug conjugate in preclinical multiple myeloma” https://doi.org/10.18632/oncotarget.28074
Research Paper - “Multipeptide stimulated PBMCs generate TEM/TCM for adoptive cell therapy in multiple myeloma” https://doi.org/10.18632/oncotarget.28067
Research Paper - “NEDD8-activating enzyme inhibition induces cell cycle arrest and anaphase catastrophe in malignant T-cells” https://doi.org/10.18632/oncotarget.28063
Research Paper - “Safety and initial efficacy of ablative radioembolization for the treatment of unresectable intrahepatic cholangiocarcinoma” https://doi.org/10.18632/oncotarget.28060
Review - “Switching Hedgehog inhibitors and other strategies to address resistance when treating advanced basal cell carcinoma” https://doi.org/10.18632/oncotarget.28080
Editorial - “Fibrocytes in primary myelofibrosis” https://doi.org/10.18632/oncotarget.27971 (PDF Download)
Research Perspective - “Ras-p53 genomic cooperativity as a model to investigate mechanisms of innate immune regulation in gastrointestinal cancers” https://doi.org/10.18632/oncotarget.27983
Keywords - cytokine profiling, breast cancer, colorectal cancer, colon cancer, lung cancer, multiple myeloma (MM), cellular therapy, T-cell lymphoma, cholangiocarcinoma, basal cell carcinoma, myelofibrosis, gastrointestinal cancer, cancer, science, research, oncology
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget
Oncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Nutrigenomics is the scientific study of the relationship between nutrition, health and the human genome. Nutritional benefits from dark, leafy greens are not merely limited to eliminating free radicals and reducing inflammation—they may also protect our DNA and slow tumor growth. Research reveals that sulforaphane (SFN), a chemical compound found in cruciferous vegetables (such as broccoli, brussels sprouts and cabbage), is capable of activating the expression of several cellular protective genes.
“The phytochemical and bioactive agent sulforaphane (SFN) has nutrigenomic potential in activating the expression of several cellular protective genes via the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2).”
Researchers have previously evaluated the nutrigenomic potential of this compound in combination with a carbonic anhydrase inhibitor drug, acetazolamide (AZ), to treat cancers, including bladder cancer and lung bronchial carcinoids (BCs). BCs are rare, well-differentiated and malignant neuroendocrine tumors (NETs). When combined, these compounds were found to significantly inhibit the viability, clonogenicity and in vitro growth of two BC cell lines.
In a new study, researchers—from The Hospital for Sick Children, University of Massachusetts, Queen’s University, IRCCS Casa Sollievo della Sofferenza, University of Chicago, Q.P.S. Holdings LLC, University of Toronto, Indian Institute of Technology Guwahati, and the Forsyth Institute—investigated the mechanisms modulated by SFN, AZ and by SFN and AZ combined, using in vitro and in vivo models of BC cell lines. Their paper was published by Oncotarget in 2021 and entitled, “Next-generation multimodality of nutrigenomic cancer therapy: sulforaphane in combination with acetazolamide actively target bronchial carcinoid cancer in disabling the PI3K/Akt/mTOR survival pathway and inducing apoptosis.”
Full blog - https://www.oncotarget.org/2021/09/21/compound-in-cruciferous-vegetables-inhibits-cancer-cells/
Press release - https://www.oncotarget.com/news/pr/disabling-the-pi3k-akt-mtor-survival-pathway-and-inducing-apoptosis/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28011
DOI - https://doi.org/10.18632/oncotarget.28011
Full text - https://www.oncotarget.com/article/28011/text/
Correspondence to - Herman Yeger - hermie@sickkids.ca, Reza Bayat Mokhtari - rbm7@queensu.ca, and Myron R. Szewczuk - szewczuk@queensu.ca
Keywords - sulforaphane, acetazolamide, bronchial carcinoid tumors, serotonin, carbonic anhydrase
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget Volume 11, Issue 27 published "Epigenetic feedback and stochastic partitioning during cell division can drive resistance to EMT" by Jia et al. which reported that Epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition are central to metastatic aggressiveness and therapy resistance in solid tumors.
While molecular determinants of both processes have been extensively characterized, the heterogeneity in the response of tumor cells to EMT and MET inducers has come into focus recently, and has been implicated in the failure of anti-cancer therapies.
Recent experimental studies have shown that some cells can undergo an irreversible EMT depending on the duration of exposure to EMT-inducing signals.
While the irreversibility of MET, or equivalently, resistance to EMT, has not been studied in as much detail, evidence supporting such behavior is slowly emerging.
Here, the authors' identify two possible mechanisms that can underlie resistance of cells to undergo EMT: epigenetic feedback in ZEB1/GRHL2 feedback loop and stochastic partitioning of biomolecules during cell division.
Identifying the ZEB1/GRHL2 axis as a key determinant of epithelial-mesenchymal plasticity across many cancer types, the authors' use mechanistic mathematical models to show how GRHL2 can be involved in both the above mentioned processes, thus driving an irreversible MET. This study highlights how an isogenic population may contain subpopulation with varying degrees of susceptibility or resistance to EMT, and proposes a next set of questions for detailed experimental studies characterizing the irreversibility of MET/resistance to EMT.
Dr. Herbert Levine from The Center for Theoretical Biological Physics at Rice University as well as The Department of Physics at Northeastern University and Dr. Mohit Kumar Jolly from The Centre for BioSystems Science and Engineering at The Indian Institute of Science said "Epithelial-Mesenchymal Transition (EMT) is a cell biological process involved in driving cancer metastasis and therapy resistance?the two grand clinically unsolved challenges."
These hybrid E/M phenotypes may drive collective cell migration as clusters of tumor cells and can be more aggressive than cells in pure epithelial or mesenchymal phenotypes.
Recent experiments decoding the dynamics of EMT/MET using live-cell imaging and/or induction and withdrawal of various EMT-inducing external signals such as TGF? or tuning the levels of EMT-specific transcription factors have provided important insights into the reversibility of EMT and MET. Cells induced to undergo EMT for shorter durations may revert to an epithelial state after withdrawal of the signal/stimulus.
However, similar investigations about the irreversibility of MET, or in other words, the resistance of epithelial cells to undergo EMT in response to EMT-inducing signals, remain to be done.
Here, the authors' propose two independent mechanism that may explain the resistance of epithelial tumor cells to undergo EMT:
1) epigenetic feedback mediated via GRHL2?an MET-inducing transcription factor ; and 2) stochastic partitioning of parent cell biomolecules among the daughter cells at the time of cell division. Conversely, here, the authors' show that incorporating this epigenetic feedback loop acting on the inhibition of ZEB1 by GRHL2 can cause an irreversible MET. Cells undergoing irreversible MET may exhibit resistance in undergoing EMT when exposed to EMT-inducing signals.
The Levine/Jolly Research Team concluded in their Oncotarget Research Paper that their results offer mechanistic insights into two possible mechanisms that may drive varying degrees of susceptibility and resistance to undergoing EMT in response to an EMT-inducing signal in a given isogenic population.
DOI - https://doi.org/10.18632/oncotarget.27651
Picture the human body’s immune response as analogous to the action of an army of military soldiers. For the most part, a healthy immune system can “hold down the fort” and protect the body from many perils of the outside world. We often rely on our immune system’s discretion to determine when and which invaders our soldiers (T cells, for example) should attack. However, when it comes to fighting the most dangerous and formidable opponents, including cancer, researchers have invested in developing new immunotherapies to help boost the body’s own immune response.
One method of immunotherapy drug delivery is liposomal nanoparticles. Natural liposomes are spherical sacs that contain phospholipids; liposomes can also be formed artificially to carry drugs and other substances into tissues. A new immunotherapy technology using liposomal nanoparticles was recently developed, called a nanoparticle-based T cell engager (nanoTCE).
“We have previously developed a nanoparticle-based T cell engagers (nanoTCEs) technology that is based on conjugation of two monoclonal antibodies (mAbs) to the surface of a liposomal nanoparticle; one antibody is against a cancer antigen and the other is against the CD3 receptor on T cells.”
The nanoTCE is a highly customizable technology that combines T cell activation with targeted cancer therapy. Researchers, from Washington University School of Medicine and Washington University McKelvey School of Engineering, claim that this highly specific technology can be engineered to engage with any immune cell to target and treat any cancer of interest. The team conducted a study using the nanoTCE technology in the treatment of acute myeloid leukemia (AML). Their paper was published on the cover of Oncotarget’s Volume 12, Issue 19, and entitled, “Nanoparticle T cell engagers for the treatment of acute myeloid leukemia.”
Full blog - https://www.oncotarget.org/2021/09/15/new-study-nanoparticles-target-acute-myeloid-leukemia/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28054
DOI - https://doi.org/10.18632/oncotarget.28054
Full text - https://www.oncotarget.com/article/28054/text/
Correspondence to - Abdel Kareem Azab - kareem.azab@wustl.edu
Keywords - acute myeloid leukemia, T cell engagers, nanoparticles, 3D tissue culture model
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to summaries of the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 19. https://www.oncotarget.com/archive/v12/i19/
Cover Paper - “Nanoparticle T cell engagers for the treatment of acute myeloid leukemia” https://doi.org/10.18632/oncotarget.28054
News - “Old drug, new trick: proton pump inhibitors find new purpose in cancer care” https://doi.org/10.18632/oncotarget.28053 (PDF Download)
Research Paper - “Novel insights into the molecular mechanisms underlying risk of colorectal cancer from smoking and red/processed meat carcinogens by modeling exposure in normal colon organoids” https://doi.org/10.18632/oncotarget.28058
Research Paper - “Altered glucuronidation deregulates androgen dependent response profiles and signifies castration resistance in prostate cancer” https://doi.org/10.18632/oncotarget.28059
Research Paper - “The antitumoral effects of chemerin are independent from leukocyte recruitment and mediated by inhibition of neoangiogenesis” https://doi.org/10.18632/oncotarget.28056
Research Paper - “Exploratory comparisons between different anti-mitotics in clinically-used drug combination in triple negative breast cancer” https://doi.org/10.18632/oncotarget.28068
Research Paper - “High expression of Myosin 1g in pediatric acute lymphoblastic leukemia” https://doi.org/10.18632/oncotarget.28055
Case Report - “Polyclonal on- and off-target resistance mutations in an EML4-ALK positive non-small cell lung cancer patient under ALK inhibition” https://doi.org/10.18632/oncotarget.28062
Research Perspective - “Towards precision oncology in angiosarcomas using next generation “omic” technologies” https://doi.org/10.18632/oncotarget.27996
Research Perspective - “Targeting AP-1 transcription factors by CRISPR in the prostate” https://doi.org/10.18632/oncotarget.27997
Research Perspective - “The role of dynamic phenotypes in cancer” https://doi.org/10.18632/oncotarget.28006
Keywords - colon organoids, acute myeloid leukemia, prostate cancer, chemerin, KIF11 inhibition, breast cancer, acute lymphoblastic leukemia, ALK inhibitors, rare cancer, dynamic phenotype, Lung cancer, cancer, science, research, oncology
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget
Oncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget recently published "Evaluations of CRC2631 toxicity, tumor colonization, and genetic stability in the TRAMP prostate cancer model" which reported that the toxicological, tumor-targeting, and efficacy profiles of Salmonella enterica serovar Typhimurium CRC2631 in a syngeneic and autochthonous TRAMP model of aggressive prostate cancer.
CRC2631 preferentially colonize primary and metastatic tumors in the TRAMP animals.
In addition, longitudinal whole genome sequencing studies of CRC2631 recovered from prostate tumor tissues demonstrate that CRC2631 is genetically stable.
Combination of CRC2631 with checkpoint blockade reduces metastasis burden.
Collectively, these Oncotarget findings demonstrate a potential for CRC2631 in cancer immunotherapy strategies.
Dr. Yves C. Chabu from The University of Missouri said, "Conventional cancer chemotherapies are not specific and, as such, generate significant morbidities."
Several bacterial strains have been developed, including the Salmonella enterica serovar Typhimurium strain VNP20009, one of the most studied tumor-targeting strains.
VNP20009 was first isolated in a genetic screen for hyper invasion mutants using a library of mutant strains derived from ultraviolet and chemical mutagenesis of strain 14028.
CRC2631 was derived from a parent strain that was derived from the prototrophic wild-type Salmonella typhimurium LT2 strain.
This collection consists of mutant strains that arose naturally under nutrient-limiting conditions for over four decades, generating a wealth of genetically diverse and potentially attenuated strains.
Similar to prostate cancers in men, these murine carcinomas disseminate throughout visceral organs, differentiate into neuroendocrine prostate cancer, and ultimately kill the host.
The Chabu Research Team concluded in their Oncotarget Research Paper, "Importantly, CRC2631 reduced metastasis incidence in the setting of checkpoint blockade. This is significant because metastasis is the main cause of cancer-associated deaths and no effective immunotherapy against prostate cancer currently exist."
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27769
Full text - https://www.oncotarget.com/article/27769/text/
Correspondence to - Yves C. Chabu - chabuc@missouri.edu
Keywords - salmonella, cancer targeting, prostate cancer, immunotherapy, TRAMP
About Oncotarget
Oncotarget is a biweekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Copyright © 2021 Impact Journals, LLC Impact Journals is a registered trademark of Impact Journals, LLC
Oncotarget recently published "Evaluations of CRC2631 toxicity, tumor colonization, and genetic stability in the TRAMP prostate cancer model" which reported that the toxicological, tumor-targeting, and efficacy profiles of Salmonella enterica serovar Typhimurium CRC2631 in a syngeneic and autochthonous TRAMP model of aggressive prostate cancer.
CRC2631 preferentially colonize primary and metastatic tumors in the TRAMP animals.
In addition, longitudinal whole genome sequencing studies of CRC2631 recovered from prostate tumor tissues demonstrate that CRC2631 is genetically stable.
Combination of CRC2631 with checkpoint blockade reduces metastasis burden.
Collectively, these Oncotarget findings demonstrate a potential for CRC2631 in cancer immunotherapy strategies.
Dr. Yves C. Chabu from The University of Missouri said, "Conventional cancer chemotherapies are not specific and, as such, generate significant morbidities."
Several bacterial strains have been developed, including the Salmonella enterica serovar Typhimurium strain VNP20009, one of the most studied tumor-targeting strains.
VNP20009 was first isolated in a genetic screen for hyper invasion mutants using a library of mutant strains derived from ultraviolet and chemical mutagenesis of strain 14028.
CRC2631 was derived from a parent strain that was derived from the prototrophic wild-type Salmonella typhimurium LT2 strain.
This collection consists of mutant strains that arose naturally under nutrient-limiting conditions for over four decades, generating a wealth of genetically diverse and potentially attenuated strains.
Similar to prostate cancers in men, these murine carcinomas disseminate throughout visceral organs, differentiate into neuroendocrine prostate cancer, and ultimately kill the host.
The Chabu Research Team concluded in their Oncotarget Research Paper, "Importantly, CRC2631 reduced metastasis incidence in the setting of checkpoint blockade. This is significant because metastasis is the main cause of cancer-associated deaths and no effective immunotherapy against prostate cancer currently exist."
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27769
Full text - https://www.oncotarget.com/article/27769/text/
Correspondence to - Yves C. Chabu - chabuc@missouri.edu
Keywords - salmonella, cancer targeting, prostate cancer, immunotherapy, TRAMP
About Oncotarget
Oncotarget is a biweekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Copyright © 2021 Impact Journals, LLC Impact Journals is a registered trademark of Impact Journals, LLC
When it comes to the mechanisms of tumor growth, the differences between epithelial and mesenchymal cell types are important to note. Normal epithelial cells are uniform, stationary and structured to bind together—forming a type of lining on/in organs (such as the outer layer of the skin), some cavities and blood vessels throughout the body. Normal mesenchymal cells are differentiated into a variety of mature cell types, including connective tissue, cartilage, lymphatic tissue, bone tissues, and etc.
Remarkably, these cells are capable of swapping phenotypes (given proper stimulation) and making epithelial-to-mesenchymal (and mesenchymal-to-epithelial) transitions (EMT). After the process of EMT, the former epithelial cells lose their cell-to-cell capacity and are endowed with migratory and invasive mesenchymal traits—with the potential to differentiate into a variety of cell lines. This process not only occurs in normal cells, but also in cancer cells. EMT enables cancer cells to transition into fluid mesenchymal traits and out of ridged and vulnerable epithelial phenotypes. Researchers believe that oxygen deprivation (hypoxia) at the core of solid tumors contributes to stimulating the formation of new vascular networks (neoangiogenesis), which induces the process of EMT to turn cancer cells stem-like.
“Hypoxia stimulates neoangiogenesis, promoting tumor outgrowth, and triggers the epithelial-mesenchymal transition (EMT), which bestows cells with mesenchymal traits and multi-lineage differentiation potential.”
However, researchers have not yet established a direct connection between the induction of EMT and the onset of neoangiogenesis in vivo. From The University of Texas MD Anderson Cancer Center, Texas A&M University, and Hamamatsu University School of Medicine, researchers conducted a study to determine whether cells undergoing EMT in a hypoxic environment “can acquire endothelial cell attributes and augment tumor growth by directly contributing to the tumor vasculature.” The proliferation of endothelial cells forms new blood vessels. Signals from endothelial cells can organize the growth and development of new endothelial cells. In April of 2021, the team published a research paper with Oncotarget on the significance of their study results, entitled, “Carcinoma cells that have undergone an epithelial-mesenchymal transition differentiate into endothelial cells and contribute to tumor growth.”
Full blog - https://www.impactjournals.com/journals/blog/oncotarget/trending-with-impact-mesenchymal-stem-cells-promote-neoangiogenesis/
Press release - https://www.oncotarget.com/news/pr/epithelial-mesenchymal-transitions-create-endothelial-cells-tumor-growth/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27940
DOI - https://doi.org/10.18632/oncotarget.27940
Full text - https://www.oncotarget.com/article/27940/text/
Correspondence to - Tapasree Roy Sarkar - tsarkar@bio.tamu.edu
Keywords - angiogenesis, endothelial transdifferentiation, epithelial-mesenchymal transition, vasculogenic mimicry, FOXC2
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Most people are aware by now that exercise has positive effects in “healthy” individuals and in patients with cancer. In cancer patients, exercise has been shown to reduce adverse events, improve quality-of-life and respiratory fitness, and even decrease the risk of breast cancer recurrence. These results, and many others, have prompted major national and international cancer organizations to make exercise recommendations.
“There also is a growing body of evidence that exercise may directly alter the tumor microenvironment to influence tumor growth, metastasis, and response to anticancer therapies.”
However, scientists and researchers have only scratched the surface of understanding the extent of the benefits that are capable of being harnessed by exercise. While research shows that exercise may impact tumors, the exercise prescription needed to induce these beneficial tumor-related outcomes is still unclear. In an effort to better harness the benefits of exercise, researchers from the University of Florida conducted a study on the effects of wheel running in breast cancer mouse models and chemotherapy. Their paper was published as the cover of Oncotarget’s Volume 12, Issue 18, and entitled, “Normal tissue and tumor microenvironment adaptations to aerobic exercise enhance doxorubicin anti-tumor efficacy and ameliorate its cardiotoxicity in retired breeder mice.”
“The goal of this study was to characterize the exercise prescription by evaluating the aerobic adaptations in both the normal tissue and the tumor microenvironment. Moreover, doxorubicin was used to assess the adjuvant effects of aerobic exercise on chemotherapy efficacy and toxicity.”
Full blog - https://www.impactjournals.com/journals/blog/oncotarget/new-study-how-exercise-boosted-chemotherapy-in-mice/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28057
DOI - https://doi.org/10.18632/oncotarget.28057
Full text - https://www.oncotarget.com/article/28057/text/
Correspondence to - Zachary R. Wakefield - zwakefield@ufl.edu
Keywords - aerobic exercise, breast cancer, hypoxia, doxorubicin, cardiotoxicity
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 18. https://www.oncotarget.com/archive/v12/i18/
Priority Research Paper (Cover) - “Normal tissue and tumor microenvironment adaptations to aerobic exercise enhance doxorubicin anti-tumor efficacy and ameliorate its cardiotoxicity in retired breeder mice” https://doi.org/10.18632/oncotarget.28057
Research Paper - “Selinexor, a selective inhibitor of nuclear export, enhances the anti-tumor activity of olaparib in triple negative breast cancer regardless of BRCA1 mutation status” https://doi.org/10.18632/oncotarget.28047
Research Paper - “Pim kinase inhibitor co-treatment decreases alternative non-homologous end-joining DNA repair and genomic instability induced by topoisomerase 2 inhibitors in cells with FLT3 internal tandem duplication” https://doi.org/10.18632/oncotarget.28042
Research Paper - “Impact factor and citation metrics in phase III cancer trials” https://doi.org/10.18632/oncotarget.28044
Research Paper - “Inhibition of the MAP2K7-JNK pathway with 5Z-7-oxozeaenol induces apoptosis in T-cell acute lymphoblastic leukemia” https://doi.org/10.18632/oncotarget.28040
Research Paper - “Correlation between PD-L1 expression and MET gene amplification in patients with advanced non–small-cell lung cancer and no other actionable oncogenic driver” https://doi.org/10.18632/oncotarget.28045
Research Paper - “Effect of hypertension and medication use regularity on postoperative delirium after maxillofacial tumors radical surgery” https://doi.org/10.18632/oncotarget.28048
Review - “Anti-aging: senolytics or gerostatics (unconventional view)” https://doi.org/10.18632/oncotarget.28049
Case Report - “The value of comprehensive genomic sequencing to maximize the identification of clinically actionable alterations in advanced cancer patients: a case series” https://doi.org/10.18632/oncotarget.28046
Editorial - “Juvenile polyposis without a germline variant in SMAD4/BMPR1A: defining a clinically distinct polyposis syndrome” https://doi.org/10.18632/oncotarget.28023 (PDF Download)
Research Perspective - “Targeting cancer stem cells via integrin β4” https://doi.org/10.18632/oncotarget.27977
Keywords - aerobic exercise, breast cancer, selinexor, Pim kinase, journal impact factor, T-ALL, non–small-cell lung cancer, oral tumor surgery, geroscience, senolytics, RNA sequencing, cancer stem cells, cancer, science, research, oncology
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget
Oncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget published "Carcinoma cells that have undergone an epithelial-mesenchymal transition differentiate into endothelial cells and contribute to tumor growth" which reported that the authors investigated whether EMT can confer endothelial attributes upon carcinoma cells, augmenting tumor growth and vascularization.
Hypoxic regions, demarcated by HIF-1α staining, exhibited focal areas of E-cadherin loss and elevated levels of vimentin and the EMT-mediator FOXC2. Implantation of MCF-7 cells, co-mixed with human mammary epithelial cells overexpressing the EMT-inducer Snail, markedly potentiated tumor growth and vascularization, compared with MCF-7 cells injected alone or co-mixed with HMLE-vector cells.
Intra-tumoral vessels contained CD31-positive cells derived from either donor cell type.
FOXC2 knockdown abrogated the potentiating effects of HMLE-Snail cells on MCF-7 tumor growth and vascularization, and compromised endothelial transdifferentiation of mesenchymal cells cultured in endothelial growth medium.
Hence, cells that have undergone EMT can promote tumor growth and neovascularization either indirectly, by promoting endothelial transdifferentiation of carcinoma cells, or directly, by acquiring an endothelial phenotype, with FOXC2 playing key roles in these processes.
A fourth mechanism—termed vasculogenic mimicry—entails the de novo generation of microvessels, lined with highly invasive tumor cells embedded in a rich extracellular matrix, essentially mimicking a true vascular endothelium and, notably, lacking in the endothelial cell markers CD31 and CD34.
Finally, newly formed blood vessels may emerge through transdifferentiation of neoplastic or tumor stem-like cells into CD31-positive endothelial-like cells, as has been documented in neuroblastoma, B-cell lymphoma, and glioblastoma.
In addition, subcutaneous injection of B16 melanoma cells into Foxc2 haploinsufficient mice has been shown to lead to the impaired formation of tumor blood vessels and, accordingly, compromise tumor growth.
Given the inherent plasticity of cells that have undergone EMT and the involvement of hypoxia in EMT and angiogenesis, the authors sought to ascertain whether cells, undergoing EMT in the hypoxic milieu, can acquire endothelial cell attributes and augment tumor growth by directly contributing to the tumor vasculature.
These findings findings link the stemness, conferred through EMT, to the acquisition of endothelial cell traits and the augmentation of tumor angiogenesis in a FOXC2-dependent manner.
The Sarkar Research Team concluded in their Oncotarget Research Output that their findings are consistent with the notion that the phenotypic attributes of cells within growing tumors are eminently pliable and that, as tumor size and the oxygen deficit increase, carcinoma cells become progressively dedifferentiated towards a mesenchymal, stem-like phenotype.
DOI - https://doi.org/10.18632/oncotarget.27940
Oncotarget published "Carcinoma cells that have undergone an epithelial-mesenchymal transition differentiate into endothelial cells and contribute to tumor growth" which reported that the authors investigated whether EMT can confer endothelial attributes upon carcinoma cells, augmenting tumor growth and vascularization.
Hypoxic regions, demarcated by HIF-1α staining, exhibited focal areas of E-cadherin loss and elevated levels of vimentin and the EMT-mediator FOXC2. Implantation of MCF-7 cells, co-mixed with human mammary epithelial cells overexpressing the EMT-inducer Snail, markedly potentiated tumor growth and vascularization, compared with MCF-7 cells injected alone or co-mixed with HMLE-vector cells.
Intra-tumoral vessels contained CD31-positive cells derived from either donor cell type.
FOXC2 knockdown abrogated the potentiating effects of HMLE-Snail cells on MCF-7 tumor growth and vascularization, and compromised endothelial transdifferentiation of mesenchymal cells cultured in endothelial growth medium.
Hence, cells that have undergone EMT can promote tumor growth and neovascularization either indirectly, by promoting endothelial transdifferentiation of carcinoma cells, or directly, by acquiring an endothelial phenotype, with FOXC2 playing key roles in these processes.
A fourth mechanism—termed vasculogenic mimicry—entails the de novo generation of microvessels, lined with highly invasive tumor cells embedded in a rich extracellular matrix, essentially mimicking a true vascular endothelium and, notably, lacking in the endothelial cell markers CD31 and CD34.
Finally, newly formed blood vessels may emerge through transdifferentiation of neoplastic or tumor stem-like cells into CD31-positive endothelial-like cells, as has been documented in neuroblastoma, B-cell lymphoma, and glioblastoma.
In addition, subcutaneous injection of B16 melanoma cells into Foxc2 haploinsufficient mice has been shown to lead to the impaired formation of tumor blood vessels and, accordingly, compromise tumor growth.
Given the inherent plasticity of cells that have undergone EMT and the involvement of hypoxia in EMT and angiogenesis, the authors sought to ascertain whether cells, undergoing EMT in the hypoxic milieu, can acquire endothelial cell attributes and augment tumor growth by directly contributing to the tumor vasculature.
These findings findings link the stemness, conferred through EMT, to the acquisition of endothelial cell traits and the augmentation of tumor angiogenesis in a FOXC2-dependent manner.
The Sarkar Research Team concluded in their Oncotarget Research Output that their findings are consistent with the notion that the phenotypic attributes of cells within growing tumors are eminently pliable and that, as tumor size and the oxygen deficit increase, carcinoma cells become progressively dedifferentiated towards a mesenchymal, stem-like phenotype.
DOI - https://doi.org/10.18632/oncotarget.27940
Lantern Pharma (a pharmaceutical company developing targeted cancer therapies) created a new drug candidate and next generation member of the acylfulvene class of prodrugs, named LP-184. Researchers from Lantern Pharma and REPROCELL (a commercial contract research organization) conducted a study to test the anti-tumor activity of this preclinical compound in a variety of NSCLC cell lines. In 2021, Oncotarget published the research paper the team authored, entitled, “The acylfulvene alkylating agent, LP-184, retains nanomolar potency in non-small cell lung cancer carrying otherwise therapy-refractory mutations.”
Despite its highly-synthetic sounding name, LP-184’s lead product (Illudins) is derived from, you guessed it, Jack-o-Lantern mushrooms.
“Acylfulvenes have been derived from cytotoxic agents called Illudins, isolated from Jack-o-Lantern mushroom (Omphalotus illudens), that retain and improve the cytotoxicity of parent Illudins for use as anticancer agents.”
The anti-tumor activity of this compound is based on activation through reductive mechanisms when metabolized, mediated by enzymes such as Prostaglandin Reductase 1 (PTGR1). PTGR1 is known to be upregulated in some tumors, including tumors with mutations in the gene KEAP1. Researchers investigated LP-184 sensitivity in NSCLC cell lines with individual or combined gene mutations in KEAP1, KRAS, TP53, and STK11.
“There is a high unmet need for effective therapies for NSCLC harboring mutations in these genes that have not only been considered undruggable till date but also are associated with loss of efficacy or resistance to multiple therapeutic strategies, at least in frontline regimens.”
LP-184 was tested in vitro in 19 primary and metastatic NSCLC cell lines to determine the range of NSCLC settings that this compound might work best in. Clinical data analyses were also conducted by the researchers to predict tumor responsiveness to LP-184. In addition, the compound was examined in two mouse models of primary lung cancer. Mouse models were tested for sensitivity to LP-184 in both two- and three-dimensional culture systems.
“We sought to assess LP-184 activity in a panel of selected NSCLC adenocarcinoma cell lines, determine associations between genomic and transcriptomic profiles and responses of cell lines tested, and compare in vitro potency of LP-184 with that of approved chemotherapy agents.”
Full blog - https://www.impactjournals.com/journals/blog/oncotarget/trending-with-impact-promising-non-small-cell-lung-cancer-prodrug/
Press release - https://www.oncotarget.com/news/pr/retaining-nanomolar-potency-in-lung-cancer-with-therapy-refractory-mutations/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632/oncotarget.27943
DOI - https://doi.org/10.18632/oncotarget.27943
Full text - https://www.oncotarget.com/article/27943/text/
Correspondence to - Aditya Kulkarni - aditya@lanternpharma.com
Keywords - non-small cell lung cancer, acylfulvene, alkylating agent, PTGR1, LP-184
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
In 2019, a study published in Oncotarget showed a C. elegans cancer screening test could detect pancreatic tumors in mice. In 2021, a team of researchers from Osaka University and Hirotsu Bio Science Inc. sought to employ this clinical tactic in the context of early pancreatic cancer detection in humans. Their paper was published as the cover of Oncotarget’s Volume 12, Issue, 17, and entitled, “Scent test using Caenorhabditis elegans to screen for early-stage pancreatic cancer.”
“Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest diseases, with a five-year survival rate of 9%.”
In this study, 83 pancreatic cancer patients from clinics in Japan participated in an open-label pilot study. Participant age, sex, pathological progression, CA19-9 values, CEA values, and urine samples were collected. All data were entered into statistical analysis. Multiple concentrations and pre- and post-surgery urine were tested using the C. elegans scent test. The researchers used a well-established olfaction analysis method and simple system for observing chemotaxis called N-NOSE (Nematode-NOSE).
The assayers placed the urine in two spots on one end of the assay plates and added sodium azide in two spots on both sides. The nematodes were placed in the center of the plates and observed for 30 minutes. The engaging behavior of C. elegans toward “favorite” smells suggested a positive chemotaxis index. The samples were assayed and analyzed to assess for the presence of positive peaks in average chemotaxis indices. They found that the C. elegans gravitated toward cancer-associated scents and that this chemotaxis index could be a sensitive marker to detect early-stage pancreatic cancer.
“Given the success of the scent test in determining the presence of pancreatic cancer in patients with PDAC who showed various progressions before and after surgery, a blinded study was conducted to determine the ability of the scent test to distinguish between patients with early-stage PDAC and healthy volunteers […]”
Full blog - https://www.oncotarget.org/2021/08/18/new-study-how-worms-can-detect-early-pancreatic-cancer/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28035
DOI - https://doi.org/10.18632/oncotarget.28035
Full text - https://www.oncotarget.com/article/28035/text/
Correspondence to - Hideshi Ishii - hishii@gesurg.med.osaka-u.ac.jp
Keywords - Caenorhabditis elegans, early-stage pancreatic cancer, scent test, biomarker, diagnosis
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 17. https://www.oncotarget.com/archive/v12/i17/
Research Paper (Cover) - “Scent test using Caenorhabditis elegans to screen for early-stage pancreatic cancer” https://doi.org/10.18632/oncotarget.28035
Research Paper - “The role of circulating miRNAs and CA19-9 in pancreatic cancer diagnosis” https://doi.org/10.18632/oncotarget.28038
Research Paper - “Diverse transcriptional regulation and functional effects revealed by CRISPR/Cas9-directed epigenetic editing” https://doi.org/10.18632/oncotarget.28037
Research Paper - “The protective role of Prolyl oligopeptidase (POP) inhibition in acute lung injury induced by intestinal ischemia-reperfusion” https://doi.org/10.18632/oncotarget.28041
Research Paper - “Quantitative difference of oral pathogen between individuals with gastric cancer and individuals without cancer” https://doi.org/10.18632/oncotarget.28034
Research Paper - “Exosomal and non-exosomal miRNA expression levels in patients with HCV-related cirrhosis and liver cancer” https://doi.org/10.18632/oncotarget.28036
Review- “Role of microRNAs in glioblastoma” https://doi.org/10.18632/oncotarget.28039
Editorial - “Mantle cell lymphoma patients in first relapse: we pretty much know what to do” https://doi.org/10.18632/oncotarget.27980 (PDF Download)
Editorial - “UBE2T: A new molecular regulator of cancer stemness in hepatocellular carcinoma” https://doi.org/10.18632/oncotarget.28033 (PDF Download)
Research Perspective - “Hypofractionation: less is more?” https://doi.org/10.18632/oncotarget.28023
Keywords - Caenorhabditis elegans, pancreatic cancer, microRNA, biomarkers, DNA methylation, acute lung injury (ALI), periodontal disease, gastric cancer, miRNA, liver cancer, glioblastoma, cancer, science, research, oncology
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget
Oncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget published this trending research perspective on June 22, 2021, entitled, "Association of high-sensitivity C-reactive protein and odds of breast cancer by molecular subtype: analysis of the MEND study" by researchers from Duke University, Durham, NC; University of Lagos, Lagos State, Nigeria; Obafemi Awolowo University Teaching Hospital, Ile-Ife, Osun State, Nigeria; University College Hospital, University of Ibadan, Ibadan, Oyo State, Nigeria; Federal Medical Center, Abeokuta, Ogun State, Nigeria; UNC Gillings School of Global Public Health, Chapel Hill, NC; Our Lady of Apostle Catholic Hospital, Ibadan, Oyo State, Nigeria; University of Alabama at Birmingham, AL; University of Kentucky, Lexington, KY; University of Kansas Medical Center, Kansas City, KS.
In this study, 555 Nigerian participants were assembled—of which 296 were confirmed breast cancer cases, and 259 were controls. The researchers collected clinical and reproductive characteristics of each participant, including the controls. In their first analysis, the researchers observed that newly diagnosed cases of Nigerian breast cancer were significantly more likely to have high levels of highly-sensitive CRP (hsCRP) compared to the controls. After adjusting for socio-demographic, clinical, and reproductive variables, the team still observed significant statistical significance for high levels of hsCRP associated with Nigerian BC. The findings from this cohort study also showed that high hsCRP was associated with a four-fold increased odds of BC.
“We also provide novel evidence of associations between hsCRP and BC molecular subtypes, with significant associations observed for luminal A, TN, and HER-enriched subtypes.”
Full blog - https://www.oncotarget.org/2021/08/12/trending-with-impact-analysis-of-breast-cancer-in-nigerian-women/
Press release - https://www.oncotarget.com/news/pr/oncotarget-odds-of-breast-cancer-by-molecular-subtype-analysis-of-the-mend-study/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27991
DOI - https://doi.org/10.18632/oncotarget.27991
Full text - https://www.oncotarget.com/article/27991/text/
Correspondence to - Tomi Akinyemiju - tomi.akinyemiju@duke.edu
Keywords - C-reactive protein, breast cancer, Nigeria, molecular subtype, menopausal status
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget published "The acylfulvene alkylating agent, LP-184, retains nanomolar potency in non-small cell lung cancer carrying otherwise therapy-refractory mutations" which reported that KEAP1 mutant NSCLCs further activate NRF2 and upregulate its client PTGR1. LP-184, a novel alkylating agent belonging to the acylfulvene class is a prodrug dependent upon PTGR1.
The authors hypothesized that NSCLC with KEAP1 mutations would continue to remain sensitive to LP-184. LP-184 demonstrated highly potent anticancer activity both in primary NSCLC cell lines and in those originating from brain metastases of primary lung cancers.
LP-184 activity correlated with PTGR1 transcript levels but was independent of mutations in key oncogenes and tumor suppressors.
Correlative analyses of sensitivity with cell line gene expression patterns indicated that alterations in NRF2, MET, EGFR and BRAF consistently modulated LP-184 sensitivity.
These correlations were then extended to TCGA analysis of 517 lung adenocarcinoma patients, out of which 35% showed elevated PTGR1, and 40% of those further displayed statistically significant co-occurrence of KEAP1 mutations.
The gene correlates of LP-184 sensitivity allow additional personalization of therapeutic options for future treatment of NSCLC.
Dr. Aditya Kulkarni from The Lantern Pharma, Inc. said, "KEAP1, KRAS, TP53 and STK11/LKB1 are among the commonly altered genes with considerable clinical prevalence in non-small cell lung cancers (NSCLC)."
The authors profiled primary and metastatic in vitro models of NSCLC for their sensitivity to LP-184 as well as standard of care agents, evaluated gene correlates of LP-184 response, and obtained evidence on in vivo anti-tumor effect of LP-184.
Mutated KEAP1 and concomitant decreased KEAP1 activity in cancer cells induces greater nuclear accumulation of NRF2, causing enhanced transcriptional induction of antioxidants, xenobiotic metabolism enzymes, and drug efflux pumps, thereby rendering KEAP1 mutations predictive of chemotherapy resistance in NSCLC patients.
The identification of a trend toward detrimental overall survival among a subset of platinum-treated NSCLC patients harboring co-occurring KRAS and STK11 mutations could label a more aggressive molecular subtype of NSCLC.
They therefore investigated LP-184 sensitivity in NSCLC cell lines harboring individual or concomitant mutations in KEAP1, KRAS, TP53 and STK11.
They sought to assess LP-184 activity in a panel of selected NSCLC adenocarcinoma cell lines, determine associations between genomic and transcriptomic profiles and responses of cell lines tested, and compare in vitro potency of LP-184 with that of approved chemotherapy agents.
The Kulkarni Research Team concluded in their Oncotarget Research Output, "Our key findings demonstrate that the alkylating agent LP-184 has nanomolar potency in several NSCLC cell lines and is more potent than selected approved alkylating chemotherapeutics. Additionally, LP-184 has the potential to target tumors with elevated PTGR1 regardless of presence of other co-occurring mutations but is especially found to be effective in the background of clinically significant KEAP1 mutations. We propose further evaluation of LP-184 in multiple PTGR1 high NSCLC settings that may not necessarily be mutually exclusive, including in highly prevalent KEAP1 and KRAS mutant tumors (Figure 6), and in patients with lack of actionable targets or resistance-related genes with no effective therapy options available."
DOI - https://doi.org/10.18632/oncotarget.27943
Full text - https://www.oncotarget.com/article/27943/text/
Correspondence to - Aditya Kulkarni - aditya@lanternpharma.com
Keywords - non-small cell lung cancer, acylfulvene, alkylating agent, PTGR1, LP-184
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
Oncotarget’s cover paper this week (Volume 12, Issue 16) is entitled, "Epigenetic signatures differentiate uterine and soft tissue leiomyosarcoma," by researchers from Yale University School of Medicine, New Haven, CT.
“In this study, we performed a comprehensive analysis and compared the DNA methylation and RNA expression profiles of ULMS and STLMS samples from the TCGA-SARC study.”
First, the team identified two LMS subtypes based on their site of origin: uterine LMS (ULMS) and non-uterine soft tissue LMS (STLMS). Next, they compared their molecular landscapes using The Cancer Genome Atlas-Sarcoma (TCGA-SARC) dataset and comprehensively analyzed 27 ULMS and 53 STLMS samples. Researchers assessed for epigenetic and transcriptomic differences between ULMS and STLMS. They hoped these differences would help identify differentially methylated genes and differentially expressed genes (DEGs) in these LMS subtypes. Findings from the TCGA-SARC dataset were then compared to two independent DNA methylation datasets, GSE140686 and GSE68312.
“In this study, we performed an integrated analysis of 98 clinically derived LMS samples and 11 controls using three publicly available datasets to identify epigenetic changes which characterize LMS subtypes and may be used as clinical biomarkers and therapeutic targets.”
Datasets were then used in comparative DNA methylation analysis to compare controls with the identified epigenetic changes associated with tumorigenesis. Network and pathway analysis were performed to further characterize the differential transcription signatures between ULMS and STLMS.
Full blog - https://www.oncotarget.org/2021/08/04/epigenetic-signatures-differentiate-leiomyosarcoma-subtypes/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28032
DOI - https://doi.org/10.18632/oncotarget.28032
Full text - https://www.oncotarget.com/article/28032/text/
Correspondence to - Nita Ahuja - nita.ahuja@yale.edu
Keywords - leiomyosarcoma, epigenetics, DNA methylation, gene expression, uterine leiomyosarcoma
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 16. https://www.oncotarget.com/archive/v12/i16/
Cover Paper - “Epigenetic signatures differentiate uterine and soft tissue leiomyosarcoma” https://doi.org/10.18632/oncotarget.28032
Research Paper - “High CD39 expression is associated with the non-muscle-invasive phenotype of human bladder cancer” https://doi.org/10.18632/oncotarget.28029
Research Paper - “MiR-7-5p inhibits thyroid cell proliferation by targeting the EGFR/MAPK and IRS2/PI3K signaling pathways” https://doi.org/10.18632/oncotarget.28030
Review - “Genetic testing for homologous recombination repair (HRR) in metastatic castration-resistant prostate cancer (mCRPC): challenges and solutions” https://doi.org/10.18632/oncotarget.28015
Review - “Interactions of multidomain pro-apoptotic and anti-apoptotic proteins in cancer cell death” https://doi.org/10.18632/oncotarget.28031
Editorial - “Mechanisms of resistance to mitochondria-targeted therapy in pancreatic cancer” https://doi.org/10.18632/oncotarget.7976 (PDF Download)
Editorial - “Glucose starvation induces NADPH collapse and disulfide stress in SLC7A11high cancer cells” https://doi.org/10.18632/oncotarget.27993 (PDF Download)
Editorial - “Tumor-reactive T cells are licensed by dendritic cells located in spatially different tissues: implications for dendritic cell vaccines” https://doi.org/10.18632/oncotarget.27972 (PDF Download)
Keywords - leiomyosarcoma, epigenetics, DNA methylation, bladder cancer, pancreatic cancer, miRNA, prostate cancer, metastatic castration-resistant prostate cancer, apoptosis, glucose starvation, T cells, cancer, science, research, oncology
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget
Oncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
The Ride for Roswell is one of the nation’s largest cycling events—hosted by Roswell Park Comprehensive Cancer Center—with ambitious goals to raise awareness and funds for cancer research and patient care. This charity bike ride, based out of Buffalo, New York, has brought people together for 25 years to celebrate cancer survivors, pay tribute to lives that have been lost, and to work together to support research and find a cure.
When it opened its doors in Buffalo in 1898, Roswell Park Comprehensive Cancer Center was the first cancer research-focused institution in the world. Today, this institution is one of only four National Cancer Institute-designated comprehensive cancer centers in the state of New York. Roswell Park Comprehensive Cancer Center is ranked by U.S. News & World Report as one of the best cancer hospitals in the United States.
The Ride for Roswell started in 1989, when Mitch Flynn, owner of the advertising agency Flynn & Friends, met Katherine Gioia. Katherine was a four-year-old patient battling a rare form of cancer. After Katherine’s death, less than a year after her diagnosis, Katherine’s mother, Anne Gioia, and aunt, Donna Gioia, founded the Roswell Park Alliance Foundation in her memory to raise money for cancer research and treatment. On June 29, 1996, Mitch and Alliance Foundation staff launched the first Ride for Roswell.
In the 25 years since then, thanks to many thousands of riders and generous donations, the Ride for Roswell has raised over $60 million to fund cancer research. The event has become one of the largest single-day charity rides in the United States.
Traditionally (excluding last year’s COVID-19 inspired “Summer of The Ride”), teams of bicyclists register to ride in a one-day event and raise money to support their participation. This summer, there are two ways to ride. Riders can join in-person at various locations (socially distanced) throughout the Western New York area on Saturday, August 7, 2021. Participants can also ride on their own throughout the month of August.
Impact Journals has been sponsoring the Ride for Roswell since 2018. The Impact Journals peloton, Team Open Access (named after the open-source online medical journals Oncotarget, Aging, Genes & Cancer, and Oncoscience), is captained by Sergei Kurenov. Sergei (who has been riding in the event since 2016) works at the Roswell Park Comprehensive Cancer Center to create, develop, and implement innovative diagnostic and surgical pre-planning software used in cancer treatment.
“Roswell Park Comprehensive Cancer Center is dedicated to providing a high level of care for cancer patients,” Sergei said. “By contributing to the Ride for Roswell, we are helping our patients to fight this most dangerous disease.”
There is still time to join Team Open Access and the Ride for Roswell this summer. You can also support the team by giving a donation of any size. Any avenue of support you may choose to donate to the Ride for Roswell will make a difference and change lives.
“Finding a cure for cancer is something we are all incredibly passionate about, and we are so thankful and grateful for your support,” Sergei said. “Together, we can make a difference!”
Team page - https://give.roswellpark.org/site/TR/SpecialEvents/General?team_id=7581&pg=team&fr_id=1660
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Biomarkers are any measurement in the body that can indicate disease, infection, or effects of the environment. These indicators are commonly used to reveal disease, but they can also be used to support personalized cancer therapy.
“In recent years, there has been an increased focus on personalized cancer therapy. One important aspect is the identification of key biomarkers that support a given treatment plan.”
Multiple biomarkers have been identified in breast cancers as helpful tools to guide targeted therapies, including the expression of HER2 and estrogen and progesterone receptors. In triple-negative breast cancer (TNBC), a number of distinct biomarkers have given rise to new targeted therapies, such as EGFR antibodies, AKT inhibitors, and PARP inhibitors.
In a well-read paper from Immunomedics, Inc. (recently acquired by Gilead Sciences, Inc.), researchers analyzed sacituzumab govitecan (SG; Trodelvy™) in TNBC. The team authored a research paper that was published by Oncotarget in 2020, and entitled, “Predictive biomarkers for sacituzumab govitecan efficacy in Trop-2-expressing triple-negative breast cancer.” To date, this paper has scored an Altmetric Attention score of 48.
“Here we examined the potential role of biomarkers in predicting the efficacy of SG.”
Sacituzumab govitecan is an antibody-drug conjugate that targets human trophoblast cell-surface antigen-2 (Trop-2)ーwhich is a glycoprotein that is commonly overexpressed in many solid tumor types.
“Trop-2 is a 46 KDa transmembrane glycoprotein that is overexpressed on many solid tumor types and is correlated with an overall poor prognosis in patients, making it an attractive target for therapy [7, 9].”
The researchers examined a highly invasive and aggressive TNBC cell line (MDA-MB-231), which is not responsive to SG, and compared their findings to TNBC cell lines that are responsive to SG. Their goal was to determine how Trop-2 expression and the homologous recombination repair (HRR) pathway (through Rad51 expression) play roles in protecting the MDA-MB-231 cell line from SG mediated DNA damage.
Trop-2 expression in transfected MDA-MB-231 and tumor xenografts were assessed, in vitro and in vivo Rad51 expression and DNA damagewere assessed via western blot, and statistical analysis was carried out for data from in vivo therapy studies.
“Trop-2 expression levels as a positive, primary biomarker and HRR proficiency as a secondary, negative biomarker were assessed in vitro and in vivo.”
Full blog: https://www.impactjournals.com/journals/blog/oncotarget/biomarker-predicts-treatment-efficacy-in-triple-negative-breast-cancer/
Press release - https://www.oncotarget.com/news/pr/predictive-biomarkers-in-trop-2-expressing-triple-negative-breast-cancer/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27766
DOI - https://doi.org/10.18632/oncotarget.27766
Full text - https://www.oncotarget.com/article/27766/text/
Correspondence to - Thomas M. Cardillo - tcardillo@immunomedics.com
Keywords - sacituzumab govitecan, Trop-2, biomarker, RAD51, triple-negative breast cancer
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget published "A novel E2F1-regulated lncRNA, LAPAS1, is required for S phase progression and cell proliferation" which reported that long non-coding RNAs are major regulators of many cellular processes, including cell cycle progression and cell proliferation.
Inhibition of LAPAS1 expression increases the percentage of S phase cells, and its silencing in synchronized cells delays their progression through S phase.
In agreement with its suggested role in cell cycle progression, prolonged inhibition of LAPAS1 attenuates proliferation of human cancer cells.
Importantly, knockdown of SPNS2 rescues the effect of LAPAS1 silencing on cell cycle and cell proliferation.
Summarily, they identify LAPAS1 as a novel E2F-regulated lncRNA that has a potential role in human cancer and regulates cell-cycle progression and cell proliferation, at least in part, via regulation of SPNS2.
Dr. Doron Ginsberg from The Bar-Ilan University said, "The human genome expresses many thousands of long non-coding RNAs (lncRNAs), which are transcripts longer than 200 bases that lack a significant open reading frame."
Increasing evidence indicates that lncRNAs are key regulators of important biological processes including cell cycle progression, cell proliferation and apoptosis.
Specifically, some lncRNAs function in regulation of cell cycle progression via modulation of critical cell cycle players, such as the cyclins, CDKs, CDK inhibitors, pRB, and p53.
Transcription factors that regulate mRNA transcription were shown to also regulate lncRNAs expression.
Inhibition of LAPAS1 expression delays progression of cells through S phase and inhibits proliferation of human cancer cells.
Thus, the authors identify LAPAS1 as a new E2F-regulated lncRNA that has a potential role in human cancer and regulates cell proliferation and cell-cycle progression, at least in part, via regulation of SPNS2.
The Ginsberg Research Team concluded in their Oncotarget Research Output, "this study reports the identification of a novel lncRNA that affects cell cycle progression and cell proliferation and may affect cancer progression. Its initial characterization shows that it is transcriptionally regulated by E2F and it exerts its activity, at least in part, by regulating SPNS2."
DOI - https://doi.org/10.18632/oncotarget.27962
Full text - https://www.oncotarget.com/article/27962/text/
Correspondence to - Doron Ginsberg - doron.ginsberg@biu.ac.il
Keywords - lncRNA, E2F, cell cycle, cell proliferation
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Copyright © 2021 Impact Journals, LLC Impact Journals is a registered trademark of Impact Journals, LLC
Oncotarget’s cover paper this week (Volume 12, Issue 15) is entitled, "Terpyridine platinum compounds induce telomere dysfunction and chromosome instability in cancer cells."
About the Study: Researchers from the National Institutes of Health, University Paris-Saclay, Kazusa DNA Research Institute, and the University of Edinburgh used a dual-Human Artificial Chromosome (HAC) assay to analyze the genomic activity of six telomere-targeting platinum compounds.
The dual-HAC assay was previously created by the researchers in this study to detect compounds that induce CIN through telomere dysfunction. This assay consists of two cell lines: one with telomeres, and one without. Disruption of the cell lines with telomeres denotes compound-induced CIN, and indicates potentially efficacious cancer therapeutics in vivo.
“Recently we developed a dual-HAC-based assay allowing quantitative comparison of the efficiency and specificity of compounds to induce telomere dysfunction [36].”
Pt-tpy, a terpyridine platinum compound, and five of its structurally modified derivatives were assayed to determine their efficacy in creating genomic instability in cancer cells via telomere disruption. The team evaluated the six compounds using two isogenic human fibrosarcoma cell lines, the dual-HAC assay, FISH analysis of EGFP-HACs, telomere fluorescent in situ hybridization (Telo-FISH), flow cytometry, calculation of the rate of spontaneous HAC loss and after compound treatment, cell viability testing for measuring HAC loss in response to drug treatment, cytokinesis-block micronucleus assay, immunofluorescence, and statistical analysis.
“We found that treatment of cancer cells with either Pt-cpym, Pt-vpym, Pt-ttpy or Pt-tpy induces telomere dysfunction leading to high levels of chromosome instability.”
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28020
DOI - https://doi.org/10.18632/oncotarget.28020
Full text - https://www.oncotarget.com/article/28020/text/
Correspondence to - Vladimir Larionov - larionov@mail.nih.gov and Natalay Kouprina - kouprinn@mail.nih.gov
Keywords - chromosome instability, CIN, platinum-derived G4-quadruplexes, telomere dysfunction, human artificial chromosome
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to summaries of the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 15. https://www.oncotarget.com/archive/v12/i15/
Cover Paper - “Terpyridine platinum compounds induce telomere dysfunction and chromosome instability in cancer cells” https://doi.org/10.18632/oncotarget.28020
Research Paper - “RNA expression differences in prostate tumors and tumor-adjacent stroma between Black and White Americans” https://doi.org/10.18632/oncotarget.28024
Research Paper - “Next-generation multimodality of nutrigenomic cancer therapy: sulforaphane in combination with acetazolamide actively target bronchial carcinoid cancer in disabling the PI3K/Akt/mTOR survival pathway and inducing apoptosis” https://doi.org/10.18632/oncotarget.28011
Research Paper - “The impact of neoadjuvant concurrent chemoradiation on exosomal markers (CD63 and CD9) expression and their prognostic significance in patients with rectal adenocarcinoma” https://doi.org/10.18632/oncotarget.28025
Research Paper - “Identification of miR-203a, mir-10a, and miR-194 as predictors for risk of lymphovascular invasion in head and neck cancers” https://doi.org/10.18632/oncotarget.28022
Research Paper - “JunD accentuates arecoline-induced disruption of tight junctions and promotes epithelial-to-mesenchymal transition by association with NEAT1 lncRNA” https://doi.org/10.18632/oncotarget.28026
Research Paper - “Actionability evaluation of biliary tract cancer by genome transcriptome analysis and Asian cancer knowledgebase” https://doi.org/10.18632/oncotarget.28021
Editorial - “Multidisciplinary clinics in prostate cancer” https://doi.org/10.18632/oncotarget.27984 (PDF Download)
Research Perspective - “Developing next generation immunomodulatory drugs and their combinations in multiple myeloma” https://doi.org/10.18632/oncotarget.27973
Keywords - chromosome instability, prostate cancer, sulforaphane, exosomes, head and neck cancer, miRNA, arecoline, biliary tract cancer, multiple myeloma, cancer, science, research, oncology
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget
Oncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget published this trending research paper on May 1, 2018, entitled, "Treatment of ovarian cancer by targeting the tumor stem cell-associated carbohydrate antigen, Sialyl-Thomsen-nouveau" by researchers from the Massachusetts General Hospital, Boston, MA; Siamab Therapeutics, Inc., Newton, MA; Harvard Medical School, Boston, MA.
Abstract: Recurrent ovarian cancer (OvCa) is thought to result in part from the inability to eliminate rare quiescent cancer stem cells (CSCs) that survive cytotoxic chemotherapy and drive tumor resurgence. The Sialyl-Thomsen-nouveau antigen (STn) is a carbohydrate moiety present on protein markers of CSCs in pancreatic, colon, and gastric malignancies. We have demonstrated that human OvCa cell lines contain varying levels of cells that independently express either STn or the ovarian CSC marker CD133. Here we determine co-expression of STn and CD133 in a subset of human OvCa cell lines. Analyses of colony and sphere forming capacity and of response to standard-of-care cytotoxic therapy suggest a subset of OvCa STn+ cells display some CSC features. The effect of the anti-STn antibody-drug conjugates (ADCs) S3F-CL-MMAE and 2G12-2B2-CL-MMAE on OvCa cell viability in vitro and in vivo was also assessed. Treatment with S3F-CL-MMAE reduced the viability of two of three OvCa cell lines in vitro and exposure to either S3F-CL-MMAE or 2G12-2B2-CL-MMAE reduced OVCAR3-derived xenograft volume in vivo, depleting STn+ tumor cells. In summary, STn+ cells demonstrate some stem-like properties and specific therapeutic targeting of STn in ovarian tumors may be an effective clinical strategy to eliminate both STn+ CSC and STn+ non-CSC populations.
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.25289
DOI - https://doi.org/10.18632/oncotarget.25289
Full text - https://www.oncotarget.com/article/25289/text/
Correspondence to - Bo R. Rueda - brueda@mgh.harvard.edu
Keywords - ovarian cancer, sialyl-Tn, antibody-drug conjugate, cancer stem cell, tumor-associated carbohydrate antigen
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget has started a new venture to expand our reach and connect with other relevant platforms using TrendMD. The TrendMD widget has been applied at the bottom of all research papers on Oncotarget.com to serve recommended content to our readers, and readers on thousands of other high-traffic websites and scholarly platforms. Recommended content is based on the content currently being viewed, content that has been viewed in the past, and content other similar readers are viewing.
“[TrendMD’s] recommendation algorithms continuously optimize the placements of links to your content for the right audience while readers are actively looking for something interesting to discover.” —Source: TrendMD.com
This platform uses algorithms similar to those that Amazon uses to help bring fresh new relevant content to interested readers. The TrendMD widget recommends content both derived from Oncotarget.com and from other biomedical journals and articles publishing similar content. They also use collaborative filtering and track user behavior to learn how to suggest the right content for the right people.
Oncotarget also uses TrendMD to help authors better circulate their research to targeted audiences around the world, cross-promote papers in adjacent fields, and increase paper citations. In a research study by Scientometrics, TrendMD was shown to outperform PubMed related citations by 272%. By joining this platform, Oncotarget publications are now incorporated into the TrendMD network—with 100 million total monthly users. Papers published by Oncotarget will now be recommended on hundreds of other leading peer-reviewed journals and scholarly websites.
“TrendMD is the world’s leading discovery platform, delivering over 1 billion recommendations to over 100 million unique users each month on 4,500 websites from over 300 scholarly publishers.” —Source: TrendMD.com
Since papers are recommended based on algorithms aiming to share specific content with readers who are most likely to be interested in the content, readership and engagement with TrendMD is very high. TrendMD statistics show that readers have the lowest bounce rate and view more content on TrendMD compared to Google AdWords, Google Scholar, Twitter, and PubPeer. Oncotarget is proud to offer this service for our authors and the scientific research community.
Keywords - research, open access, publications, journals, papers
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
This week's cover paper of Oncotarget (Volume 12, Issue 14) is entitled, "Esomeprazole enhances the effect of ionizing radiation to improve tumor control," by researchers from Baylor College of Medicine, University of Texas MD Anderson Cancer Center, and Texas Children’s Hospital.
Abstract: The resistance of cancer cells to radiation-based treatment is a major clinical challenge confounding standard of care in cancer. This problem is particularly notable in many solid tumors where cancer cells are only partially responsive to radiation therapy. Combination of radiation with radiosensitizers is able to enhance tumor cell killing. However, currently available radiosensitizers are associated with significant normal tissue toxicity. Accordingly, there is an unmet need to develop safer and more effective radiosensitizers to improve tumor control. Here, we evaluated the radiosensitizing effect of the FDA-approved drug esomeprazole in normal and radioresistant human head and neck squamous cell carcinoma (HNSCC) cells in vitro, and in a mouse model of HNSCC. For the in vitro studies, we used cancer cell colony formation (clonogenicity) assay to compare cancer cell growth in the absence or presence of esomeprazole. To determine mechanism(s) of action, we assessed cell proliferation and profiled cell cycle regulatory proteins. In addition, we performed reverse phase protein array (RPPA) study to understand the global effect of esomeprazole on over 200 cancer-related proteins. For the in vivo study, we engrafted HNSCC in a mouse model and compared tumor growth in animals treated with radiation, esomeprazole, and combination of radiation with esomeprazole. We found that esomeprazole inhibits tumor growth and dose-dependently enhances the cell killing effect of ionizing radiation in wildtype and p53-mutant radioresistant cancer cells. Mechanistic studies demonstrate that esomeprazole arrests cancer cells in the G1 phase of the cell cycle through upregulation of p21 protein and inhibition of cyclin-dependent kinases (Cdks) type 1 (Cdk1) and type 2 (Cdk2). In vivo data showed greater tumor control in animals treated with combination of radiation and esomeprazole compared to either treatment alone, and that this was associated with inhibition of cell proliferation in vivo. In addition, combination of esomeprazole with radiation significantly impaired repair following radiation-induced DNA damage. Our studies indicate that esomeprazole sensitizes cancer cells to ionizing radiation, and is associated with upregulation of p21 to arrest cells in the G1 phase of the cell cycle. Our findings have significant therapeutic implications for the repurposing of esomeprazole as a radiosensitizer in HNSCC and other solid tumors.
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28008
DOI - https://doi.org/10.18632/oncotarget.28008
Full text - https://www.oncotarget.com/article/28008/text/
Correspondence to - Yohannes T. Ghebre - yohannes.ghebre@bcm.edu
Keywords - esomeprazole, proton pump inhibitors, ionizing radiation, radiosensitization, tumor control
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to short summaries of the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 14. https://www.oncotarget.com/archive/v12/i14/
Cover Paper - “Esomeprazole enhances the effect of ionizing radiation to improve tumor control” https://doi.org/10.18632/oncotarget.28008
Research Paper - “Mebendazole disrupts stromal desmoplasia and tumorigenesis in two models of pancreatic cancer” https://doi.org/10.18632/oncotarget.28014
Research Paper - “MRI texture features from tumor core and margin in the prediction of response to neoadjuvant chemotherapy in patients with locally advanced breast cancer” https://doi.org/10.18632/oncotarget.28002
Research Paper - “The use of a uPAR-targeted probe for photothermal cancer therapy prolongs survival in a xenograft mouse model of glioblastoma” https://doi.org/10.18632/oncotarget.28013
Research Paper - “Eltrombopag and its iron chelating properties in pediatric acute myeloid leukemia” https://doi.org/10.18632/oncotarget.28000
Research Paper - “Prokineticin-1 induces normal lymphangiogenic activity and is involved in lymphangiogenesis and lymph node metastasis in colorectal cancer” https://doi.org/10.18632/oncotarget.28016
Research Paper - “Appropriate body mass index cutoffs for type 2 diabetes in Xinjiang population: defining the influence of liver aminotransferase” https://doi.org/10.18632/oncotarget.28009
Review - “Multifaceted effect of chlorpromazine in cancer: implications for cancer treatment” https://doi.org/10.18632/oncotarget.28010
Research Perspective - “Targeting cancer associated fibroblasts to enhance immunotherapy: emerging strategies and future perspectives” https://doi.org/10.18632/oncotarget.27936
Research Perspective - “A Dynamic Energy Budget (DEB) based modeling framework to describe tumor-in-host growth inhibition and cachexia onset during anticancer treatment in in vivo xenograft studies” https://doi.org/10.18632/oncotarget.27960
Keywords - mebendazole, pancreatic cancer, esomeprazole, tumor control, MRI, breast cancer, eltrombopag, colorectal cancer, AML, type 2 diabetes, chlorpromazine, immunotherapy, tumors, cancer, science, research, oncology
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget
Oncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget published "TRAIL receptor agonists convert the response of breast cancer cells to ONC201 from anti-proliferative to apoptotic" which reported normal fibroblasts do not undergo apoptosis following rhTRAIL plus ONC201. In vivo, MDA-MB-361 tumor growth rate is significantly reduced following treatment with a combination of ONC201 and rhTRAIL as compared to control tumors.
Natural killer cells which use TRAIL to kill DR5-expressing cancer cells, exhibit greater cytotoxicity against ONC201-treated breast cancer cells compared to controls.
rhTRAIL also converts the response of cells from other tumor types to ONC201 from anti-proliferative to apoptotic.
A monoclonal DR5-agonistic antibody converts the response of non-TNBC cells to ONC201 from anti-proliferative to apoptotic.
These Oncotarget findings describe a novel therapeutic strategy that potently converts the response of a cancer cell to ONC201 from anti-proliferative to apoptotic.
Dr. Wafik S. El-Deiry Founding Editorial Board Member of Oncotarget said, "Breast cancer is the most commonly diagnosed cancer and is the number three cause of cancer-related death in United States women."
The potential of TRAIL to kill cancerous cells while leaving normal cells unharmed led to the development and clinical testing of TRAIL-based therapies such as recombinant human TRAIL and death receptor agonistic antibodies.
ONC201 potently induced cell death through the extrinsic pathway in cancer cells from a variety of tumor types.
The compound is unique in that it is a dual activator of the TRAIL pathway, able not only to upregulate pro-death ligand TRAIL, but also its receptor DR5. Early studies of the mechanism of action of ONC201 showed that the compound inhibited pro-survival kinases Akt and ERK, leading to the dephosphorylation and activation of transcription factor FOXO3a.
Previous work has shown that ONC201 is a potent dual inducer of the TRAIL pathway at the level of both the ligand and the receptor, and that breast cancers show decreased sensitivity to TRAIL .
The authors hypothesized that profiling the effects of the compound on the TRAIL pathway in breast cancer and identifying blocks in signal transduction would allow us to identify therapeutic strategies with the potential to induce apoptosis and that could potentially translate to tumor regressions in patients who do not respond to treatment with ONC201 alone.
The El-Deiry Research Team concluded in their Oncotarget Research Output that this team's previous data showed that in breast cancer, the anti-proliferative effects of ONC201 are more common than the apoptotic effects.
While the apoptotic effects of ONC201 led to in vivo efficacy of the compound, the anti-proliferative effects did not.
In the present study, they investigated mechanisms as well as strategies to convert the response of breast cancer cells to ONC201 from anti-proliferative to pro-apoptotic.
TRAIL receptor agonists such as rhTRAIL or a DR5-agonistic antibody convert the response of these cells to ONC201 from anti-proliferative to apoptotic.
These findings may have clinical relevance as ONC201 is currently being tested in patients with breast cancer, and the authors believe that this newly identified combinatorial strategy has the potential to induce tumor regressions in patients with limited response to ONC201 monotherapy.
DOI - https://doi.org/10.18632/oncotarget.27773
Full text - https://www.oncotarget.com/article/27773/text/
Correspondence to - Wafik S. El-Deiry - wafik@brown.edu
Keywords - ONC201, TRAIL, breast cancer, death receptors, apoptosis
Oncotarget published this trending research paper on October 20, 2020, entitled, "TRAIL receptor agonists convert the response of breast cancer cells to ONC201 from anti-proliferative to apoptotic" by researchers from Temple University, Philadelphia, PA; Fox Chase Cancer Center, Philadelphia, PA; Brown University, Providence, RI; Brown University and the Lifespan Health System, Providence, RI.
Abstract: ONC201 was initially identified as an inducer of cell death through the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway. The compound is currently being tested in patients with hematological malignancies and solid tumors, including those of the breast. We investigated strategies to convert the response of breast cancers to ONC201 from anti-proliferative to apoptotic. ONC201 treatment upregulates TRAIL and primes TRAIL-resistant non-triple negative breast cancer (TNBC) cells to undergo cell death through the extrinsic pathway. Remarkably, the addition of exogenous recombinant human TRAIL (rhTRAIL) converts the response of TRAIL-resistant non-TNBC cells to ONC201 from anti-proliferative to apoptotic in a death receptor 5 (DR5)-dependent manner in vitro. Importantly, normal fibroblasts do not undergo apoptosis following rhTRAIL plus ONC201. In vivo, MDA-MB-361 tumor growth rate is significantly reduced following treatment with a combination of ONC201 and rhTRAIL as compared to control tumors. Natural killer (NK) cells which use TRAIL to kill DR5-expressing cancer cells, exhibit greater cytotoxicity against ONC201-treated breast cancer cells compared to controls. rhTRAIL also converts the response of cells from other tumor types to ONC201 from anti-proliferative to apoptotic. A monoclonal DR5-agonistic antibody converts the response of non-TNBC cells to ONC201 from anti-proliferative to apoptotic. Our findings describe a novel therapeutic strategy that potently converts the response of a cancer cell to ONC201 from anti-proliferative to apoptotic. This approach may be clinically relevant and has potential to induce tumor regression of patient tumors with relative resistance to ONC201 monotherapy.
Press release - https://www.oncotarget.com/news/pr/breast-cancer-cells-to-onc201-from-anti-proliferative-to-apoptotic/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27773
DOI - https://doi.org/10.18632/oncotarget.27773
Full text - https://www.oncotarget.com/article/27773/text/
Correspondence to - Wafik S. El-Deiry - wafik@brown.edu
Keywords - ONC201, TRAIL, breast cancer, death receptors, apoptosis
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
This week's cover paper of Oncotarget (Volume 12, Issue 13) is entitled, "Oncogenic transformation of NIH/3T3 cells by the overexpression of L-type amino acid transporter 1, a promising anti-cancer target," by researchers from Kindai University, Higashiosaka-Shi, Osaka, Japan; Tohoku University, Sendai-Shi, Miyagi, Japan; Tokyo University of Science, Noda-shi, Chiba, Japan; Hyogo University of Health Sciences, Kobe-Shi, Hyogo, Japan.
Abstract: L-type amino acid transporter 1 (LAT1)/SLC7A5 is the first identified CD98 light chain disulfide linked to the CD98 heavy chain (CD98hc/SLC3A2). LAT1 transports large neutral amino acids, including leucine, which activates mTOR, and is highly expressed in human cancers. We investigated the oncogenicity of human LAT1 introduced to NIH/3T3 cells by retrovirus infection. NIH/3T3 cell lines stably expressing human native (164C) or mutant (164S) LAT1 (naLAT1/3T3 or muLAT1/3T3, respectively) were established. We confirmed that endogenous mouse CD98hc forms a disulfide bond with exogenous human LAT1 in naLAT1/3T3, but not in muLAT1/3T3. Endogenous mouse CD98hc mRNA increased in both naNIH/3T3 and muLAT1/3T3, and a similar amount of exogenous human LAT1 protein was detected in both cell lines. Furthermore, naLAT1/3T3 and muLAT1/3T3 cell lines were evaluated for cell growth-related phenotypes (phosphorylation of ERK, cell-cycle progression) and cell malignancy-related phenotypes (anchorage-independent cell growth, tumor formation in nude mice). naLAT1/3T3 had stronger growth- and malignancy- related phenotypes than NIH/3T3 and muLAT1/3T3, suggesting the oncogenicity of native LAT1 through its interaction with CD98hc. Anti-LAT1 monoclonal antibodies significantly inhibited in vitro cell proliferation and in vivo tumor growth of naLAT1/3T3 cells in nude mice, demonstrating LAT1 to be a promising anti-cancer target.
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27981
DOI - https://doi.org/10.18632/oncotarget.27981
Full text - https://www.oncotarget.com/article/27981/text/
Correspondence to - Takashi Masuko - masuko@phar.kindai.ac.jp
Keywords - CD98, LAT1, monoclonal antibody, NIH/3T3, oncogenicity
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to short summaries of the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 13. https://www.oncotarget.com/archive/v12/i13/
Cover Paper “Oncogenic transformation of NIH/3T3 cells by the overexpression of L-type amino acid transporter 1, a promising anti-cancer target” https://doi.org/10.18632/oncotarget.27981
News “A new class of radiosensitizers for glioblastoma” https://doi.org/10.18632/oncotarget.27970 (PDF Download)
Research Paper “A platform for locoregional T-cell immunotherapy to control HNSCC recurrence following tumor resection” https://doi.org/10.18632/oncotarget.27982
Research Paper “Human papilloma virus circulating tumor DNA assay predicts treatment response in recurrent/metastatic head and neck squamous cell carcinoma” https://doi.org/10.18632/oncotarget.27992
Research Paper “Association of high-sensitivity C-reactive protein and odds of breast cancer by molecular subtype: analysis of the MEND study” https://doi.org/10.18632/oncotarget.27991
Research Paper “Glucocorticoid receptor antagonism promotes apoptosis in solid tumor cells” https://doi.org/10.18632/oncotarget.27989
Research Paper “TERT and its binding protein: overexpression of GABPA/B in high grade gliomas” https://doi.org/10.18632/oncotarget.27985
Review “Cross-talks in colon cancer between RAGE/AGEs axis and in-flammation/immunotherapy” https://doi.org/10.18632/oncotarget.27990
Review “Cancer-epigenetic function of the histone methyltransferase KMT2D and therapeutic opportunities for the treatment of KMT2D-deficient tumors” https://doi.org/10.18632/oncotarget.27988
Research Perspective “Targeting super-enhancers reprograms glioblastoma central carbon metabolism” https://doi.org/10.18632/oncotarget.27938
Editorial Perspective “Polo-like kinase inhibition as a therapeutic target in acute myeloid leukemia” https://doi.org/10.18632/oncotarget.27919 (PDF Download)
Editorial “The formation of pre-effectors in the steady state opens a new perspective for cancer immunosurveillance” https://doi.org/10.18632/oncotarget.27967 (PDF Download)
Editorial “Mechanisms of gefitinib-induced interstitial pneumonitis: why and how the TKI perturbs innate immune systems?” https://doi.org/10.18632/oncotarget.27958 (PDF Download)
Keywords - oncogenicity, glioblastoma, head and neck cancer, immunotherapy, tumors, glioma, colon cancer, epigenetics, cancer immunosurveillance, gefitinib, AML, breast cancer, cancer, science, research, oncology
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget
Oncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget published this trending research paper on March 30, 2021, entitled, "Inhibition of resistant triple-negative breast cancer cells with low-dose 6-mercaptopurine and 5-azacitidine" by researchers from the University of Texas MD Anderson Cancer Center, Houston, Texas.
Triple-negative breast cancer (TNBC) accounts for 10-15% of all breast cancers. “Triple-negative” refers to the lack of HER2 protein and estrogen and progesterone receptors. This means that TNBC cannot be treated with hormone inhibition and must be treated with conventional chemotherapy. In addition, many of these highly adaptable breast cancer cells can opportunistically switch between proliferation and quiescence. This highly-heterogeneous cancer is very difficult to treat, and TNBC patients frequently develop drug resistance and relapse after neoadjuvant therapies.
The researchers from the University of Texas MD Anderson Cancer Center conducted a research study in hopes of developing a safe and effective therapeutic combination to treat resistant triple-negative breast cancer.
“Evidence suggests that SUM149-metabolic adaptable (MA) cells are a suitable model of resistant human triple-negative breast cancer (TNBC) cells that can survive bottlenecks in the body, including therapeutic interventions, by opportunistically switching between quiescence and cell proliferation.”
In this in vitro study, researchers cultured three highly drug-resistant and metastatic progenitor-like TNBC cell lines with a difficult phenotype—opportunistic switching between quiescence and proliferation. Researchers focused on designing a safe treatment that is effective in both low- and high-risk patients. The researchers note that it was critical to their study that the regimen is proven safe to administer to patients for early use in the minimal residual disease (MRD) stage after surgery, and before clinical metastasis is detected.
“For a potential therapy to be suitable at the MRD stage, it must be safe (an important criterion prior to clinical relapse) and disrupt heterogeneous progenitor-like cancer cells that evolve into clinical metastases.”
Two chemotherapy and immunosuppressive drugs (ribonucleoside analogues) were tested on the cell lines at low doses for the sake of viability in the MRD stage: 6-mercaptopurine (6-MP) and 5-azacitidine (5-AzaC). Both of these drugs have been clinically proven to be well-tolerated and to have drug-sensitizing, quiescence-stabilizing, and apoptosis-inducing effects in cancer cells.
“We chose 5-AzaC because it could complement 6-MP’s effects on the transcriptome and epigenome, and—as indicated by many Phase 1 clinical trials—5-AzaC is well tolerated.”
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27922
DOI - https://doi.org/10.18632/oncotarget.27922
Full text - https://www.oncotarget.com/article/27922/text/
Correspondence to - Anthony Lucci - alucci@mdanderson.org and Balraj Singh - bsingh@mdanderson.org
Keywords - resistant TNBC, minimal residual disease, intratumor heterogeneity, breast cancer relapse, metastasis prevention
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
In this week's cover paper of Oncotarget (Volume 12, Issue 12), entitled, "Frame-shift mediated reduction of gain-of-function p53 R273H and deletion of the R273H C-terminus in breast cancer cells result in replication-stress sensitivity," researchers used the CRISPR-Cas9 tool to analyze a p53 mutation in triple-negative breast cancer.
The researchers from the City University of New York, Columbia University, and Weill Cornell Medical College wrote that both the C-terminal domain (CTD) and oligomerization domain (OD) of mtp53 R273H proteins are intact, and it is not clear if these regions are responsible for chromatin-based DNA replication activities. To examine the ability of mtp53 R273H to influence cell proliferation, DNA replication, and cell cycle progression of breast cancer cells, the researchers used the CRISPR-Cas9 tool to edit the C-terminal regions of the mtp53 gene.
“CRISPR-Cas9 sgRNA editing of the C-terminal regions of the endogenous mtp53 gene were carried out so as to delete gene sequences that correspond to the OD and CTD regions.”
The team generated breast cancer cells and edited CTD and OD regions of mtp53 R273H using the CRISPR-Cas9 tool. They then treated the cell populations with thymidine—to block cells at G1/S phase in the cell cycle. The researchers then compared the status and proliferation of the variants with the original cell line and observed changes in total cell lysates by western blot analysis.
“We examined how changes in the level of mtp53 R273H level and/or deletion of the CTD, or OD plus CTD, region influenced cell proliferation, cell cycle progression, and chromatin association of mtp53, RPA, PCNA and MCM2.”
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27975
DOI - https://doi.org/10.18632/oncotarget.27975
Full text - https://www.oncotarget.com/article/27975/text/
Correspondence to - Jill Bargonetti - bargonetti@genectr.hunter.cuny.edu
Keywords - mutant p53, gain-of-function, oligomerization, DNA replication, frame-shift, breast cancer
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 12.
The full issue of Oncotarget: https://www.oncotarget.com/archive/v12/i12/
COVER PAPER: “Frame-shift mediated reduction of gain-of-function p53 R273H and deletion of the R273H C-terminus in breast cancer cells result in replication-stress sensitivity” https://doi.org/10.18632/oncotarget.27975
NEWS: “LY6 gene family presents a novel class of potential biomarkers associated with overall survival outcome of pancreatic ductal adenocarcinoma” https://doi.org/10.18632/oncotarget.27968 (PDF Download)
EDITORIAL: “Neoantigen evolution in head and neck cancer progression: Where do we go from here?” https://doi.org/10.18632/oncotarget.27942 (PDF Download)
EDITORIAL: “Unexpected zinc dependency of ferroptosis – what is in a name?” https://doi.org/10.18632/oncotarget.27951 (PDF Download)
RESEARCH PAPER: “Role for Fgr and Numb in retinoic acid-induced differentiation and G0 arrest of non-APL AML cells” https://doi.org/10.18632/oncotarget.27969
RESEARCH PAPER: “Dynamic cellular biomechanics in responses to chemotherapeutic drug in hypoxia probed by atomic force spectroscopy” https://doi.org/10.18632/oncotarget.27974
RESEARCH PAPER: “Genomic clustering analysis identifies molecular subtypes of thymic epithelial tumors independent of World Health Organization histologic type” https://doi.org/10.18632/oncotarget.27978
RESEARCH PAPER: “Deep learning with deep convolutional neural network using FDG-PET/CT for malignant pleural mesothelioma diagnosis” https://doi.org/10.18632/oncotarget.27979
Keywords - mutant p53, DNA replication, head and neck cancer, biomarker, ferroptosis, retinoic acid(RA), hypoxia, thymic epithelial tumor, mesothelioma, AML, breast cancer, pancreatic cancer, cancer, science, research, oncology
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget
Oncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget published this trending research paper on April 13, 2021, entitled, "Urine protein biomarkers of bladder cancer arising from 16-plex antibody-based screens" conducted by researchers from the University of Houston and UT Southwestern Medical Center.
Bladder cancer is four times more common among men than women, and it is the sixth most common cancer diagnosis in the United States. However, researchers have found that cystoscopy—the primary method physicians use to diagnose patients with bladder cancer—is relatively invasive, expensive, and has the potential to cause urinary tract infections.
“In contrast, urine is a noninvasive and readily available biological fluid that can be used for diagnostic tests.”
Patients may benefit in a number of different ways by using urine as fluid in diagnostic testing for bladder cancer. Urine is readily bioavailable, non-invasive, and it can also be collected and tested on a regular basis. Patients can even use various cost-effective point-of-care diagnostic tools, including at-home testing. First, the researchers assessed whether there were useful biomarkers of bladder cancer to be found in this fluid. The team used Luminex screening to test for both low and high levels of 16 proteins utilizing highly specific antibody-protein interactions.
“In this study, Luminex screening was used to simultaneously assay the protein abundances of 16 potential biomarkers in different stages of bladder cancer and then compared to urology clinic controls.”
ELISA validation was then used to determine which proteins were significantly elevated in bladder cancer. They found that levels of three urine proteins were capable of distinguishing between control and bladder cancer urine. One protein was also found to be capable of discriminating between high- and low-grade disease, and the successive clinical stages of bladder cancer.
“Upon ELISA validation, urine IL-1α, IL-1ra, and IL-8 were able to distinguish control urine from urine drawn from various bladder cancer stages, with IL-8 being the best discriminator.”
To date, the research paper has generated an Altmetric Attention Score of 55. The Altmetric Attention Score provides an at-a-glance indication of the volume and type of online attention the research has received.
Top Oncotarget publications rated by Altmetric Attention Score - https://www.oncotarget.com/news/altmetric/
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27941
DOI - https://doi.org/10.18632/oncotarget.27941
Full text - https://www.oncotarget.com/article/27941/text/
Correspondence to - Chandra Mohan - cmohan@central.uh.edu
Keywords - urothelial, proteomics, targeted screens, interleukins, inflammation
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
In this week's cover paper of Oncotarget (Volume 12, Issue 11) entitled, "CEA as a blood-based biomarker in anal cancer," researchers from The University of Texas – MD Anderson Cancer Center, Terasaki Foundation of Biomedical Sciences, and Vanderbilt Ingram Cancer Center conducted a retrospective, single-institution study to determine the correlation between carcinoembryonic antigen (CEA) levels (a commonly employed assay for patients with colorectal adenocarcinoma) and biopsy-proven Squamous cell carcinoma of the anal canal (SCCA).
The researchers retrospectively analyzed 219 patients who were treated at The University of Texas – MD Anderson Cancer Center between 2013 and 2020. The team collected demographic data, clinical history, and CEA levels, including gender, ethnicity, stage at initial diagnosis of SCCA, HPV status, HIV status, and smoking history. Patients with coexisting second primary cancers besides SCCA were excluded from their analysis.
The median age of patients in the study was 56 years old, 74% were female, and 89% were of Caucasian ethnicity. At the time of the initial CEA measurement, patients were at various stages of SCCA, with 39% in stage III and 41% with metastatic disease to distant organs. 67% of patients had currently or previously tested positive for HPV infection. Statistical analysis was calculated using the summarized demographic and clinical characteristics of patients as means with associated standard deviations.
“Here we report the largest series detailing the relevance of CEA as a biomarker for patients with SCCA.”
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27959
DOI - https://doi.org/10.18632/oncotarget.27959
Full text - https://www.oncotarget.com/article/27959/text/
Correspondence to - Van K. Morris - vkmorris@mdanderson.org
Keywords - carcinoembryonic antigen, squamous cell carcinoma of anal canal, anal cancer, biomarkers, HPV
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 11.
View the complete issue: https://www.oncotarget.com/archive/v12/i11/
COVER PAPER: “CEA as a blood-based biomarker in anal cancer” https://doi.org/10.18632/oncotarget.27959
NEWS: “FGFR1, a novel biomarker for metastatic castration-resistant prostate cancer?” https://doi.org/10.18632/oncotarget.27957 (PDF Download)
EDITORIAL: “Advances in innovative exosome-technology for real time monitoring of viable drugs in clinical translation, prognosis and treatment response” https://doi.org/10.18632/oncotarget.27927 (PDF Download)
EDITORIAL: “Drug-development, dose-selection, rational combinations from bench-to-bedside: are there any lessons worth revisiting?” https://doi.org/10.18632/oncotarget.27931 (PDF Download)
RESEARCH PAPER: “Occurence of RAS reversion in metastatic colorectal cancer patients treated with bevacizumab” https://doi.org/10.18632/oncotarget.27965
RESEARCH PAPER: “Caspase-11 and AIM2 inflammasome are involved in smoking-induced COPD and lung adenocarcinoma” https://doi.org/10.18632/oncotarget.27964
RESEARCH PAPER: “A novel E2F1-regulated lncRNA, LAPAS1, is required for S phase progression and cell proliferation” https://doi.org/10.18632/oncotarget.27962
RESEARCH PAPER: “Epigallocatechin-3-gallate modulates Tau Post-translational modifications and cytoskeletal network” https://doi.org/10.18632/oncotarget.27963
RESEARCH PAPER: “Ex vivo analysis of DNA repair targeting in extreme rare cutaneous apocrine sweat gland carcinoma” https://doi.org/10.18632/oncotarget.27961
REVIEW: “Evaluation of liver kinase B1 downstream signaling expression in various breast cancers and relapse free survival after systemic chemotherapy treatment” https://doi.org/10.18632/oncotarget.27929
CASE REPORT: “Immunotherapy in Xeroderma Pigmentosum: a case of advanced cutaneous squamous cell carcinoma treated with cemiplimab and a literature review” https://doi.org/10.18632/oncotarget.27966
Keywords - anal cancer, prostate cancer, colorectal cancer, lung cancer, breast cancer, exosomes, cell proliferation, Tau protein, Alzheimer’s disease, DNA repair, advanced squamous cell carcinoma, cancer, science, research, oncology
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget
Oncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Skin cancer is a highly preventable cancer (in non-hereditary cases), due to a major risk factor being prolonged exposure to ultraviolet (UV) radiation. However, skin cancer is the most commonly diagnosed cancer in the United States. By the age of 70, one in five Americans are predicted to be diagnosed with skin cancer.
There are three types of cells that are usually involved in skin cancer: basal cells, squamous cells, and melanocytes (or pigment producing cells). The type of skin cell affected by cancer is what classifies the difference between basal cell carcinoma, squamous cell carcinoma, and melanoma.
Basal cell carcinoma is the most common and most treatable form of skin cancer. Basal cell carcinomas grow slowly and cause minimal damage if detected and treated early. The second most common form of skin cancer is squamous cell carcinoma. Squamous cell carcinoma of the skin may also be termed cutaneous squamous cell carcinoma, in order to differentiate from other squamous cell cancers that may occur in the body.
Melanoma of the skin is the mutation, often followed by the rampant division, of the skin’s melanocytes. It is the most serious type of skin cancer due to its tendency to spread to other organs. Surprisingly, as much as 30% of all melanoma cases are a result of factors other* than exposure to the sun or other UV light. The causes of such cases are still unknown to researchers, but some suggest that causes could be hereditary.
Oncotarget’s Special Collection on Skin Cancer & Melanoma is intended to be a tool for researchers and science readers alike to learn more about the current landscape of skin cancer. The creators of these collections are hopeful that this resource may help researchers discover new biomarkers, mechanisms, and therapies that improve our collective quality of life and lead to enhanced treatments for cancer and other diseases.
Papers within this Special Collection relate to various topics on skin cancer research, including a 2018 paper from Australia on the first blood test for early detection of melanoma, a paper by researchers from Columbia University on a combined therapeutic approach that improves anti-tumor antibody therapy in melanoma, and many more.
Read Oncotarget’s Special Collection on Skin Cancer: https://www.oncotarget.com/collections/skin-cancer/
Visit the Special Collections Archive: https://www.oncotarget.com/collections/
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget published this trending research paper on June 4, 2019, entitled, “Dissecting the role of RNA modification regulatory proteins in melanoma,” by researchers from the Department of Pathology, Yale University School of Medicine, and the Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham.
“Since RNA is a key molecule that drives every cellular process, their deregulation is present in nearly all human disease and play a causative role.”
The researchers explain that alterations among RNAs may arise due to altered activity or expression of the enzymes/proteins which are involved in the modification process. In this study, the team used multiple publicly available bioinformatics platforms to, first, analyze RNA alterations in melanoma samples, and then, to comprehensively analyze RNA modification regulatory proteins among melanoma samples. The publicly available datasets included: The Cancer Genome Atlas, The Human Protein Atlas, Oncomine, and the UALCAN database.
“Our study started with the analysis of various genetic alterations (amplifications, mutations/deletion) as well as RNA overexpression of these RNA modification regulatory proteins in The Cancer Genome Atlas melanoma database.”
Based on their analyses of these databases, reverse transcription quantitative PCR, soft-agar assays, validation by shRNA-mediated knockdown, and statistical analysis, the team identified what they believe are the most relevant RNA modifying proteins that play a crucial role in the development of melanoma. They found that METTL4 and DNMT3A RNA-modifying enzymes/proteins are both necessary for melanoma growth and overexpressed in melanoma.
“Based on this we infer that the upregulated expression of RNA modification regulatory proteins METTL4 and DNMT3A play a key role in melanoma initiation or progression.”
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.26959
DOI - https://doi.org/10.18632/oncotarget.26959
Full text - https://www.oncotarget.com/article/26959/text/
Correspondence to - Romi Gupta - romigup@uab.edu
Keywords - RNA modifications, epitranscriptome, melanoma, MAPK, BRAF mutant melanoma, skin cancer
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Scientific integrity is a crucial component of scholarly publishing. In order to consistently publish high-quality science, it is integral to have strong ethical standards for scientific and academic integrity. At Impact Journals, a growing industry of digital technologies, tools, and ideas are constantly being added to our robust scientific integrity process. Impact Journals (based out of Buffalo, New York) is an international open-access publisher of journals in the field of biomedical sciences.
The Impact Journals process to maintain scientific integrity in scientific publishing is built around several components: 1.) Publicly available ethics statements; 2.) Adherence to industry standards for scientific publishing; 3.) Diligent and insightful peer-review; 4.) Elimination of plagiarism; 5.) Image forensics service; and finally, 6.) If a problem arises post-publication, we conduct investigations following COPE guidelines in cooperation with the authors and their affiliated institution.
In addition to our diligent peer-review process, Impact Journals uses advanced image forensics service to check applicable images in all submitted papers. This service includes multiple in-house and third party tools for image screening as well as to compare newly submitted images against images found on the Internet and those that have already been published in one of our journals. You may find more details about our scientific integrity process at Oncotarget.com, under Editorial Policies.
Visit Oncotarget.com for the Editorial Policies - https://www.oncotarget.com/editorial-policies/#editorial-policies
Impact Journals is presenting our full scientific integrity process at the 2021 Society for Scholarly Publishing (SSP) Annual Meeting, occurring virtually from May 24-27, 2021.
To learn more about Impact Journals, or any of our journals, please visit www.impactjournals.com.
About Impact Journals
Impact Journals is an open-access publisher, focusing on topics surrounding cancer research, all fields of aging research, and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Our mission is to provide scientists with the opportunity to share their exceptional discoveries, offer services that enable rapid dissemination of results, and to present vital findings from the many fields of biomedical science. Our goal is life without disease.
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
In the cover paper of this week's issue of Oncotarget (Volume 12, Issue 10), titled, "Inhibitory effects of Tomivosertib in acute myeloid leukemia," researchers based out of Chicago, Illinois, U.S., from Northwestern University’s Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, and Jesse Brown Veterans Affairs Medical Center conducted a new study to assess the efficacy of Tomivosertib to regulate the eIF4E binding protein in AML.
In this study, the researchers purchased Tomivosertib (and Venetoclax) from TargetMol. They cultured AML cell lines, used clonogenic leukemic progenitor assays in methylcellulose, cell viability assays, cell lysis and immunoblotting, co-immunoprecipitation assays, plasmids and transfections, and conducted proteomics immunoprecipitation analysis using liquid-chromatography-tandem mass spectrometry, gene annotation and protein function enrichment analysis, and statistical analysis.
“We demonstrate that Tomivosertib suppresses eIF4E phosphorylation in AML cells and decreases leukemic cell survival and proliferation.”
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27952
DOI - https://doi.org/10.18632/oncotarget.27952
Full text - https://www.oncotarget.com/article/27952/text/
Correspondence to - Leonidas C. Platanias - l-platanias@northwestern.edu
Keywords - MNK, Tomivosertib, acute myeloid leukemia, eIF4E
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 10.
View the complete issue: https://www.oncotarget.com/archive/v12/i10/
COVER PAPER: “Inhibitory effects of Tomivosertib in acute myeloid leukemia” https://doi.org/10.18632/oncotarget.27952
EDITORIAL: “Raman spectroscopy determination of the mineral characteristics of microcalcifications in breast cancer, a way towards an improved screening approach” https://doi.org/10.18632/oncotarget.27912 (PDF Download)
EDITORIAL: “Reactive oxygen species in leukemias: maintaining cancer cell proliferation via redox signaling and changing metabolic homeostasis” https://doi.org/10.18632/oncotarget.27913 (PDF Download)
RESEARCH PAPER: “Genome wide DNA methylation landscape reveals glioblastoma’s influence on epigenetic changes in tumor infiltrating CD4+ T cells” https://doi.org/10.18632/oncotarget.27955
RESEARCH PAPER: “Association between miRNA signatures in serum samples from epidermal growth factor inhibitor treated patients and skin toxicity” https://doi.org/10.18632/oncotarget.27953
RESEARCH PAPER: “Perioperative changes in the plasma metabolome of patients receiving general anesthesia for pancreatic cancer surgery” https://doi.org/10.18632/oncotarget.27956
RESEARCH PAPER: “Transcriptome analyses of urine RNA reveal tumor markers for human bladder cancer: validated amplicons for RT-qPCR-based detection” https://doi.org/10.18632/oncotarget.27954
Keywords - acute myeloid leukemia, breast cancer, bladder cancer, leukemia, DNA methylation, tumor, glioblastoma, miRNA, skin toxicity, pancreatic cancer, cancer, science, research, oncology
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget
Oncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget published this trending research paper on April 13, 2021, entitled, “Insulin-like growth factor 1/Child-Turcotte-Pugh composite score as a predictor of treatment outcomes in patients with advanced hepatocellular carcinoma treated with sorafenib,” by researchers from the University of Texas MD Anderson Cancer Center, Massachusetts General Hospital, and Harvard Medical School.
The majority of circulating insulin–like growth factor (IGF) is synthesized and secreted by the liver, and levels of IGF dramatically decrease in chronic liver disease and HCC. IGF can be a helpful tool to determine the prognosis of patients with advanced HCC while undergoing treatment with sorafenib. Researchers also use the Child-Turcotte-Pugh (CTP) qualitative scoring system to assess severity of liver cirrhosis, hepatic reserve, guide treatment decisions, and to stratify patients with HCC into three groups (A, B, and C). CTP class A has a better prognosis compared to classes B and C.
“Assessing liver reserve in HCC is of a great value as a tool for stratification of patients in clinical trials as well as to predict HCC outcome and guide therapy decisions in routine practice.”
In the researchers’ prospective study, 171 patients with HCC from the University of Texas MD Anderson Cancer Center were screened and included in this study. Of the patients, 116 were classified in CTP group A. Patient IGF/CTP scores were calculated and the researchers used the Kaplan-Meier method and log-rank test to estimate and compare the time-to-event outcomes between patient subgroups. Based on CTP and the IGF/CTP scores, researchers reclassified group A patients into AA and AB risk groups, which differed significantly in terms of OS and PFS. The researchers followed up with all patients in the study until disease progression or death. Unfortunately, during the follow-up period, 100 patients passed away.
“After IGF/CTP scoring, 87 of 116 CTP class A patients were reclassified as IGF/CTP-A (AA) and 29 patients were reclassified as IGF/CTP-B (AB).”
Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27924
DOI - https://doi.org/10.18632/oncotarget.27924
Full text - https://www.oncotarget.com/article/27924/text/
Correspondence to - Ahmed O. Kaseb - akaseb@mdanderson.org
Keywords - IGF-1, Child-Pugh, sorafenib, liver reserve, hepatocellular carcinoma
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
In the cover paper of this week's issue of Oncotarget (Volume 12, Issue 9), titled, "Creation of a new class of radiosensitizers for glioblastoma based on the mibefradil pharmacophore," researchers conducted a study to create mibefradil analogs as superior radiosensitizers for glioblastomas.
In the current study, based on their previous findings, the researchers from Yale University used structure activity relationship analysis and EJ-DR assays to create, synthesize, and profile a series of 140 mibefradil analogs. Their goal was to develop superior mibefradil analogues, with reduced off-target effects and improved potency.
After successfully reducing the known off-target liabilities of mibefradil, the team selected the top 12 analogues for further in vitro and in vivo pharmacokinetic studies. These analogs were tested in vivo to verify that they cross the blood-brain barrier and accumulate in mouse brain tissue.
“We then tested the pharmacokinetic parameters of the synthesized analogues and validated their ability to cross the blood-brain barrier (BBB) and accumulate in mouse brain tissue, at levels similar to that observed with mibefradil.”
DOI - https://doi.org/10.18632/oncotarget.27933
Full text - https://www.oncotarget.com/article/27933/text/
Correspondence to - Yulia V. Surovtseva - yulia.surovtseva@yale.edu and Ranjit S. Bindra - ranjit.bindra@yale.edu
Keywords - glioblastoma, radiosensitizers, mibefradil, DNA repair, alternative non-homologous end joining
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to the latest oncology-focused research published in this week’s issue of Oncotarget, Volume 12, Issue 9.
View the complete issue: https://www.oncotarget.com/archive/v12/i9/
Oncotarget Volume 12, Issue 9 features:
COVER PAPER: “Creation of a new class of radiosensitizers for glioblastoma based on the mibefradil pharmacophore” https://doi.org/10.18632/oncotarget.27933
EDITORIAL: “Is there a role for CDK 4/6 inhibitors in breast cancer brain metastases?” https://doi.org/10.18632/oncotarget.27904 (PDF Download)
EDITORIAL: “Epigenetic effects of pharmacologic ascorbate” https://doi.org/10.18632/oncotarget.27911 (PDF Download)
RESEARCH PAPER: “Activation of plasmacytoid dendritic cells promotes AML-cell fratricide” https://doi.org/10.18632/oncotarget.27949
RESEARCH PAPER: “Piperlongumine promotes death of retinoblastoma cancer cells” https://doi.org/10.18632/oncotarget.27947
RESEARCH PAPER: “A higher De Ritis ratio (AST/ALT) is a risk factor for progression in high-risk non-muscle invasive bladder cancer” https://doi.org/10.18632/oncotarget.27944
RESEARCH PAPER: “Down regulation of lactate dehydrogenase initiates apoptosis in HeLa and MCF-7 cancer cells through increased voltage-dependent anion channel protein and inhibition of BCL2” https://doi.org/10.18632/oncotarget.27950
REVIEW: “Multigene tests for breast cancer: the physician’s perspective” https://doi.org/10.18632/oncotarget.27948
Keywords - breast cancer, bladder cancer, glioblastoma, plasmacytoid dendritic cells, pharmacologic ascorbate, retinoblastoma, cancer cells, cancer, science, research, oncology
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget
Oncotarget is published by Impact Journals, LLC. Please visit https://www.impactjournals.com/ or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget published this trending paper on July 21, 2020, entitled, “Genomic markers of midostaurin drug sensitivity in FLT3 mutated and FLT3 wild-type acute myeloid leukemia patients,” by researchers from Knight Cancer Institute, Oregon Health and Science University; Division of Hematology and Medical Oncology, Oregon Health and Science University; Howard Hughes Medical Institute; Department of Cell, Developmental, and Cancer Biology, Oregon Health and Science University.
The researchers conducted a study to identify features that may predict response to midostaurin in FLT3 mutant and wild-type samples. They performed an ex vivo drug sensitivity screen on primary and relapsed AML samples, with corresponding targeted sequencing and RNA sequencing.
In order to understand the impact that different genomic alterations have on midostaurin response, the researchers identified 214 patients with AML and annotated for their FLT3 status. Of these patients, 193 were primary and 21 were relapse AML samples from the Beat AML publicly available dataset. Risk groups within the cohort were as follows: 73 samples were favorable risk, 59 samples were intermediate, and 68 were adverse. The median age of patients in the cohort was 61, with 52% male and 48% female.
“We hypothesized that there are additional genomic alterations and gene expression changes outside of FLT3-ITD mutations that can influence AML sample resistance or sensitivity to midostaurin and aimed to further characterize these factors.”
To date, this research paper has generated an Altmetric Attention score of 54. Altmetric Attention scores, located at the top-left of trending Oncotarget papers, provide an at-a-glance indication of the volume and type of online attention the research has received.
Top Oncotarget publications rated by Altmetric score: https://www.oncotarget.com/news/altmetric/
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27656
Full text - https://www.oncotarget.com/article/27656/text/
Correspondence to - Mara W. Rosenberg - rosenberg.mara@gmail.com
Keywords - acute myeloid leukemia, drug sensitivity, midostaurin, drug resistance, FLT3
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
In the cover paper of this week's issue of Oncotarget (Volume 12, Issue 8), titled, "Prognostic and therapeutic value of the Hippo pathway, RABL6A, and p53-MDM2 axes in sarcomas," researchers examined five potential biomarkers across 18 different histologic subtypes of sarcoma in 163 tissue samples. Immunohistochemical staining, statistical analysis, and correlation-based network analysis revealed promising results.
Researchers from the University of Iowa, University of Alabama at Birmingham, and the Mayo Clinic, report the need for additional prognostic and therapeutic biomarkers to predict clinical behavior across different histological types of sarcoma.
“Although the French (FNCLCC) and NCI grading schemes have been adopted for many sarcomas, there is a substantial subset of sarcomas for which the grading scheme does not adequately predict clinical behavior.”
Sign up for free Altmetric alerts about this article:
DOI: https://doi.org/10.18632/oncotarget.27928 Full text: https://www.oncotarget.com/article/27928/text/
Correspondence to: Munir R. Tanas - munir-tanas@uiowa.edu
About Oncotarget:
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to short summaries of the latest oncology-focused research published in this week's issue of Oncotarget. https://www.oncotarget.com/archive/v12/i8/
Oncotarget Volume 12, Issue 8 features:
COVER PAPER: “Prognostic and therapeutic value of the Hippo pathway, RABL6A, and p53-MDM2 axes in sarcomas” https://doi.org/10.18632/oncotarget.27928
NEWS: “Immunotherapy and fatigue: what we know and what we don’t know” https://doi.org/10.18632/oncotarget.27946 (PDF Download)
EDITORIAL: “Drug exposure: still relevant after all these years” https://doi.org/10.18632/oncotarget.27899 (PDF Download)
EDITORIAL: “Up to your NEK2 in CIN” https://doi.org/10.18632/oncotarget.27918 (PDF Download)
RESEARCH PAPER: “Analytic validation and clinical utilization of the comprehensive genomic profiling test, GEM ExTra®” https://doi.org/10.18632/oncotarget.27945
RESEARCH PAPER: “Insulin-like growth factor 1/Child-Turcotte-Pugh composite score as a predictor of treatment outcomes in patients with advanced hepatocellular carcinoma treated with sorafenib” https://doi.org/10.18632/oncotarget.27924
RESEARCH PAPER: “Controlling for cellular heterogeneity using single-cell deconvolution of gene expression reveals novel markers of colorectal tumors exhibiting microsatellite instability” https://doi.org/10.18632/oncotarget.27935
RESEARCH PAPER: “Urine protein biomarkers of bladder cancer arising from 16-plex antibody-based screens” https://doi.org/10.18632/oncotarget.27941
RESEARCH PAPER: “The acylfulvene alkylating agent, LP-184, retains nanomolar potency in non-small cell lung cancer carrying otherwise therapy-refractory mutations” https://doi.org/10.18632/oncotarget.27943
RESEARCH PAPER: “Loss of CPAP causes sustained EGFR signaling and epithelial-mesenchymal transition in oral cancer” https://doi.org/10.18632/oncotarget.27932
RESEARCH PAPER: “Carcinoma cells that have undergone an epithelial-mesenchymal transition differentiate into endothelial cells and contribute to tumor growth” https://doi.org/10.18632/oncotarget.27940
RESEARCH PAPER: “Predicting clinical outcomes using cancer progression associated signatures” https://doi.org/10.18632/oncotarget.27934
RESEARCH PAPER: “High in vitro and in vivo synergistic activity between mTORC1 and PLK1 inhibition in adenocarcinoma NSCLC” https://doi.org/10.18632/oncotarget.27930
About Oncotarget:
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or follow us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget
Oncotarget is published by Impact Journals , LLC. Please visit https://www.impactjournals.com/ or connect with us @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Oncotarget published this trending paper on March 30, 2021, entitled, “Differential expression of Vitamin D binding protein in thyroid cancer health disparities,” researchers from Harbor-UCLA Medical Center, Loma Linda University School of Medicine, and Riverside University Health System compared the expression of DBP in patients with thyroid cancer from Filipino Americans and European Americans.
Filipino Americans are disproportionately affected by thyroid cancer, and the goal of this research was to further elucidate the functional implications of DBP in different stages of thyroid cancer across ethnicities.
“Although DBP is an essential protein with multifunctional properties, very few studies are available on its contribution to thyroid cancer oncogenesis.” Read the full study: https://www.oncotarget.com/article/27920/text/
The Trending with Impact series highlights Oncotarget publications attracting higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. More from the Trending with Impact series: https://www.oncotarget.org/tag/trending-with-impact/
Sign up for free Altmetric alerts about this article: DOI: https://doi.org/10.18632/oncotarget.27920 Full text: https://www.oncotarget.com/article/27920/text/
Correspondence to: Salma Khan - salmakhan@llu.edu
About Oncotarget:
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
In this top-performing paper published in Oncotarget on July 17, 2018, entitled, “A diagnostic autoantibody signature for primary cutaneous melanoma,” Australian researchers developed the first blood test to detect melanoma in early stages.
The researchers from Australia’s Edith Cowan University, Hollywood Private Hospital, Level 1 Melanoma, St. John of God Hospital, Dermatology Specialist Group, Skin Check WA, and The University of Western Australia collected blood sera (plural of serum, which contains exogenous substances in the blood, such as electrolytes, antibodies, autoantibodies, antigens, and hormones) from a total of 245 primary melanoma patients and healthy volunteers. The sera were screened against a high-throughput microarray profiling platform of 1,627 functional proteins. After conducting detailed statistical analysis, the team found that the most effective biomarker for melanoma diagnosis was a combined signature of 10 autoantibodies which, together, displayed 79% sensitivity and 84% specificity in primary melanoma detection.
“This melanoma autoantibody signature may prove valuable for the development of a diagnostic blood test for routine population screening that, when used in conjunction with current melanoma diagnostic techniques, could improve the early diagnosis of this malignancy and ultimately decrease the mortality rate of patients.”
To date, this research paper has since generated an impressive Altmetric Attention score of 597. Read the full study: https://www.oncotarget.com/article/25669/text/
The Top-Performer series highlights research literature published in Oncotarget that has generated a high Altmetric score. Altmetric scores, located at the top-left of trending Oncotarget papers, provide an at-a-glance indication of the volume and type of online attention the research has received. Top Oncotarget publications rated by Altmetric score: https://www.oncotarget.com/news/altmetric/ More from the Top-Performer series: https://www.oncotarget.org/tag/top-performer/
Sign up for free Altmetric alerts about this article: DOI: https://doi.org/10.18632/oncotarget.25669 Full text: https://www.oncotarget.com/article/25669/text/
Correspondence to: Pauline Zaenker - p.zaenker@ecu.edu.au; paulinez@our.ecu.edu.au
About Oncotarget:
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
In Oncotarget Volume 12, Issue 7 cover paper, titled, "Caloric restriction creates a metabolic pattern of chronological aging delay that in budding yeast differs from the metabolic design established by two other geroprotectors," the researchers conducted a study which compared the metabolic effects of three geroprotectors in budding yeast: calorie restriction, the tor1Δ mutation, and lithocholic acid.
In this study, the researchers from the Department of Biology at Concordia University in Montreal, Quebec, used chronologically aging Saccharomyces cerevisiae—a common budding yeast found in baking, winemaking, and beer brewing. S. cerevisiae is a fungus useful for measuring the mechanisms of aging. The researchers cultured S. cerevisiae in a nutrient-rich medium and compared the metabolic effects of three different geroprotective interventions (both concurrently and separately).
Using liquid chromatography and a tandem mass spectrometry method of non-targeted metabolomics, the team measured the intracellular concentrations of 193 structurally and functionally diverse water-soluble metabolites within S. cerevisiae.
“Here, we used liquid chromatography coupled with tandem mass spectrometry method of non-targeted metabolomics to compare the effects of these three geroprotectors on the intracellular metabolome of chronologically aging budding yeast.” Read the full study here: https://doi.org/10.18632/oncotarget.27926 Oncotarget Volume 12, Issue 7: https://www.oncotarget.com/archive/v12/i7/
About Oncotarget:
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or follow us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget
Oncotarget is published by Impact Journals , LLC. Please visit https://www.impactjournals.com/ or connect with us @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
The American Association for Cancer Research (AACR) organizes an annual meeting program covering some of the most recent discoveries in cancer research. The conference aims to highlight work from the best minds in research and medicine from institutions all over the world. Oncotarget, exhibited by its publisher Impact Journals, will be participating virtually at the AACR Annual Meeting this year. Visit the Oncotarget website: www.oncotarget.com Visit the Impact Journals website: www.impactjournals.com
As of June 2020, Scopus released their latest 2019 Journal Rankings on Oncology. Oncotarget is among their highest rated (Q1) journals and ranked number one in total citations in oncology. The journal has published outstanding papers and reviews by authors including Bert Vogelstein, Peter K. Vogt, Pier Paolo Pandolfi, Arnold J. Levine, Brian Druker, and Carol Prives. Founding Oncotarget Editorial Board members include Nobel Laureates Andrew V. Schally and Gregg L. Semenza; Lasker Award recipients Alexander Varshavsky, Brian J. Druker, and Gregg L. Semenza; and 16 members of the US National Academy of Sciences. Oncotarget is indexed and archived in PubMed, PubMed Central, Scopus, EMBASE, and META (Chan Zuckerberg Initiative).
The 2021 AACR conference, a two-week online event, will take place from April 10-15 and May 17-21, 2021. Topics include population science and prevention, cancer biology, translational and clinical studies, survivorship, and advocacy.
In 2019, Oncotarget participated in the AACR Annual Meeting at the Georgia World Congress Center in Atlanta, Georgia, USA, and "AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics," at the Hynes Convention Center in Boston, Massachusetts, USA. The total registration count from the 2019 AACR Annual Meeting was over 21,000—nearly 16,000 of which were scientific attendees from all over the world.
Follow the Oncotarget Twitter account (@Oncotarget) for live updates about the conference using the #AACR21 hashtag.
About Oncotarget:
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit www.oncotarget.com or follow us:
SoundCloud - @oncotarget Facebook - www.facebook.com/Oncotarget/ Twitter - twitter.com/oncotarget LinkedIn - www.linkedin.com/company/oncotarget Instagram - www.instagram.com/oncotargetjrnl/ YouTube - www.youtube.com/OncotargetYouTube Pinterest - www.pinterest.com/oncotarget/ Reddit - www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Listen to short summaries of the latest oncology-focused research published in this week's issue of Oncotarget. https://www.oncotarget.com/archive/v12/i7/
Oncotarget Volume 12, Issue 7 features:
COVER PAPER: "Caloric restriction creates a metabolic pattern of chronological aging delay that in budding yeast differs from the metabolic design established by two other geroprotectors" https://doi.org/10.18632/oncotarget.27926
EDITORIAL: "The long road to TRAIL therapy: a TRAILshort detour" https://doi.org/10.18632/oncotarget.27902
RESEARCH PERSPECTIVE: "The role of immune surveillance in malignant transformation of benign salivary gland tumors" https://doi.org/10.18632/oncotarget.27900
RESEARCH PAPER: "Differential expression of Vitamin D binding protein in thyroid cancer health disparities" https://doi.org/10.18632/oncotarget.27920
RESEARCH PAPER: "Inhibition of resistant triple-negative breast cancer cells with low-dose 6-mercaptopurine and 5-azacitidine" https://doi.org/10.18632/oncotarget.27922
RESEARCH PAPER: "Mutually exclusive lymphangiogenesis or perineural infiltration in human skin squamous-cell carcinoma" https://doi.org/10.18632/oncotarget.27915
RESEARCH PAPER: "Decreased expression of the translation factor eIF3e induces senescence in breast cancer cells via suppression of PARP1 and activation of mTORC1" https://doi.org/10.18632/oncotarget.27923
RESEARCH PAPER: "[18F]FDG and [18F]FES positron emission tomography for disease monitoring and assessment of anti-hormonal treatment eligibility in granulosa cell tumors of the ovary" https://doi.org/10.18632/oncotarget.27925
RESEARCH PAPER: "Effect of cell microenvironment on the drug sensitivity of hepatocellular cancer cells" https://doi.org/10.18632/oncotarget.27910
RESEARCH PAPER: "Landscape of somatic mutations in breast cancer: new opportunities for targeted therapies in Saudi Arabian patients" https://doi.org/10.18632/oncotarget.27909
RESEARCH PAPER: "The presence of polymorphisms in genes controlling neurotransmitter metabolism and disease prognosis in patients with prostate cancer: a possible link with schizophrenia" https://doi.org/10.18632/oncotarget.27921
CASE REPORT: "Prognostic significance of isochromosome 17q in hematologic malignancies" https://doi.org/10.18632/oncotarget.27914
About Oncotarget:
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or follow us:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/oncotargetyoutube Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget
Oncotarget is published by Impact Journals , LLC. Please visit https://www.impactjournals.com/ or connect with us @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
In a trending paper published by Oncotarget on March 2, 2021, titled, “Quantitative proteome profiling stratifies fibroepithelial lesions of the breast,” researchers from India conducted a study to better characterize phyllodes tumors and other breast fibroepithelial lesions in order to improve diagnosis and treatment for patients.
To begin identifying the differentially expressed genes and proteins among FAD and PTs in benign, borderline, and malignant states, the researchers conducted quantitative global proteomics on Formalin-Fixed Paraffin-Embedded (FFPE) tissue sections. They conducted a principal component analysis of the protein expression matrix to identify the overlapping proteomic profiles among FELs.
“Interestingly, we observed FADs and benign PTs clustered together compared to borderline and malignant ones, albeit with overlapping protein expression profiles.” Read the full study: doi.org/10.18632/oncotarget.27889 Oncotarget Volume 12, Issue 6: oncotarget.com/archive/v12/i6/
The Trending with Impact series highlights Oncotarget publications attracting higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. More from Trending with Impact: https://www.oncotarget.org/tag/trending-with-impact/
About Oncotarget:
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit www.oncotarget.com or follow us:
SoundCloud - @oncotarget Facebook - www.facebook.com/Oncotarget/ Twitter - twitter.com/oncotarget LinkedIn - www.linkedin.com/company/oncotarget Instagram - www.instagram.com/oncotargetjrnl/ YouTube - www.youtube.com/OncotargetYouTube Pinterest - www.pinterest.com/oncotarget/ Reddit - www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Oncotarget published "Quantitative proteome profiling stratifies fibroepithelial lesions of the breast" which reported that the current grading system remains unreliable in differentiating these tumors due to histological heterogeneity and lack of appropriate markers to monitor the sudden and unpredictable malignant transformation of PTs.
The high- throughput quantitative proteomic analysis suggested that FAD and PTs form distinct clusters away from borderline and malignant though there exist marked differences between them.
Interestingly, over-expression of extracellular matrices related proteins and epithelial-mesenchymal transition markers in borderline PTs led these authors to hypothesize a model of deposition and degradation leading to ECM remodeling and EMT acquisition triggering its malignant transformation.
They also identified three candidate biomarkers such as MUCL1, HTRA1, and VEGDF uniquely expressed in FAD, borderline, and malignant PTs, respectively, which were further validated using immunohistochemistry.
The present Oncotarget work shed light on a brief mechanistic framework of PTs aggressive nature and present potential biomarkers to differentiate overlapping FELs that would be of practical utility in augmenting existing diagnosis and disease management for this rare tumor.
Dr. Lekha Dinesh Kumar and Dr. Prashant Kumar both from The CSIR-Centre for Cellular and Molecular Biology said, "Fibroepithelial lesions (FELs) of the breast are a group of biphasic tumors that are highly heterogeneous in terms of their morphological as well as biological features."
FADs are widespread tumors accounting for 68% of all breast masses and 44–94% of biopsied breast lesions.
A commonly encountered complication in diagnosis is the differentiation of FADs and benign PTs primarily contributed by the overlapping histologic and morphological characteristics between these lesions.
Several recurrently mutated genes unique to FAD and PTs, and several protein markers have also been investigated previously for their diagnostic utility and association with histological grade in FELs.
However, not much effort has been made to identify potential diagnostic biomarkers that could improve the diagnostic practice to classify PTs and differentiate them from FADs.
To this end, the authors employed iTRAQ based quantitative proteomics of FELs to extensively characterize the proteomic alterations across these tumors in order to identify potential biomarkers and distinctly stratify these overlapping tumors.
The Kumar/Kumar Research Team concluded in their Oncotarget Research Output, "this study provided a comprehensive profile of differentially regulated proteins across various subtypes of FELs. The presence of extensive ECM proteins and EMT markers led us to hypothesize a model of deposition and degradation of these proteins thus triggering ECM remodeling and EMT acquisition in borderline PTs leading to its malignant state. Enrichment of platelet degranulation factors in malignant PT indicates active angiogenesis during this transformation. Herein, our initial findings suggest that MUCL1, HTRA1, and VEGFD can be used as potential proteomic markers that could augment existing diagnosis, and help in monitoring the progression of the disease. Further characterization of FELs using different omics platforms would help in better understanding of the cellular and molecular events that would help in understanding the disease dynamics and thus better management of the disease."
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27889
Full text - https://www.oncotarget.com/article/27889/text/
Correspondence to - Lekha Dinesh Kumar - lekha@ccmb.res.in and Prashant Kumar - prashant@ibioinformatics.org
Keywords - breast tumors, fibroepithelial lesions, phyllodes, iTRAQ, quantitative proteomics
In the cover paper of this week's issue of Oncotarget, titled: "Genomic and neoantigen evolution from primary tumor to first metastases in head and neck squamous cell carcinoma," the aim of the researchers in this exploratory study was to characterize the genomic and neoantigen changes in 23 paired primary and recurrent HNSCC tumors.
Of the 23 patients in this study, 17 were male and 14 were tobacco smokers. The distribution of primary tumor location was nine in the oral cavity, seven in the oropharynx, six in the larynx, and one in the hypopharynx. The researchers note that all seven patients with an oropharyngeal primary tumor were HPV+. All 23 patients received some combination of traditional treatment.
“To understand the recurrent mutation effect between primary and recurrent/metastatic tumors, we extract recurrently mutated genes (>1 sample mutated gene) from primary and recurrent/metastatic samples, separately.” Read the full study here: https://doi.org/10.18632/oncotarget.27907 Oncotarget Volume 12, Issue 6: https://www.oncotarget.com/archive/v12/i6/
About Oncotarget:
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit www.oncotarget.com or follow us:
SoundCloud - @oncotarget Facebook - www.facebook.com/Oncotarget/ Twitter - twitter.com/oncotarget LinkedIn - www.linkedin.com/company/oncotarget Instagram - www.instagram.com/oncotargetjrnl/ YouTube - www.youtube.com/OncotargetYouTube Pinterest - www.pinterest.com/oncotarget/ Reddit - www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Listen to short summaries of the latest oncology-focused research literature published in this week's issue of Oncotarget. https://www.oncotarget.com/archive/v12/i6/
Oncotarget Volume 12, Issue 6 features:
COVER PAPER: "Genomic and neoantigen evolution from primary tumor to first metastases in head and neck squamous cell carcinoma."
Institutions: Washington University in St. Louis, Columbia University, St. Louis Children’s Hospital, Siteman Cancer Center
Quote: “We characterized genomic and neoantigen changes between 23 paired primary and recurrent HNSCC tumors. Twenty-three biopsies from patients originally diagnosed with locally advanced disease were identified from the Washington University tumor bank.” doi.org/10.18632/oncotarget.27907
EDITORIAL: "Innovating and expanding weight loss strategies for breast cancer survivors."
Institution: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Quote: “Compared to those with ideal body weight, women who have excess weight experience inferior outcomes once diagnosed with breast cancer, despite standard local and adjuvant therapy [6].” https://doi.org/10.18632/oncotarget.27898
RESEARCH PERSPECTIVE: "Pancreatic cancer driver mutations are targetable through distant alternative RNA splicing dependencies."
Institutions: The Johns Hopkins University School of Medicine, Dartmouth Geisel School of Medicine and Norris Cotton Cancer Center, Yale University, Stony Brook University Renaissance School of Medicine
Quote: “Here, we review PDAC pathogenesis as it relates to fundamental ARS [Alternative RNA splicing] biology, with an extension to implications for PDAC patient clinical management.” doi.org/10.18632/oncotarget.27901
RESEARCH PAPER: "A high-content AlphaScreen™ identifies E6-specific small molecule inhibitors as potential therapeutics for HPV+ head and neck squamous cell carcinomas."
Institutions: Loma Linda University, University of Kansas
Quote: “Herein we describe our search for small molecule inhibitors that disrupt binding of E6 to caspase 8 using AlphaScreen technology™ (Perkin Elmer, Waltham, MA). This technology is a proximity-based platform for identifying hit compounds that perturb a specific interaction between two beaded proteins. Using this approach, we interrogated a library of over 5000 small molecules for compounds that antagonize E6 binding to caspase 8.” doi.org/10.18632/oncotarget.27908
RESEARCH PAPER: "Characterization of the inflammatory microenvironment and hepatic macrophage subsets in experimental hepatocellular carcinoma models."
Institution: Ghent University
Quote: “Here, we characterized the tumor microenvironment and the proportion and transcriptional profile of hepatic macrophages (Mφ) in two commonly used HCC mouse models.” doi.org/10.18632/oncotarget.27906
RESEARCH PAPER: "Molecular characterization of lung squamous cell carcinoma tumors reveals therapeutically relevant alterations."
Institutions: Tata Memorial Centre, Homi Bhabha National Institute
Quote: “We performed survival analyses of lung squamous cell carcinoma patients harboring therapeutically relevant alterations identified by whole exome sequencing and mass spectrometry-based validation across 430 lung squamous tumors.” doi.org/10.18632/oncotarget.27905
About Oncotarget:
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit www.oncotarget.com or follow us:
SoundCloud - @oncotarget Facebook - www.facebook.com/Oncotarget/ Twitter - twitter.com/oncotarget LinkedIn - www.linkedin.com/company/oncotarget Instagram - www.instagram.com/oncotargetjrnl/ YouTube - www.youtube.com/OncotargetYouTube Pinterest - www.pinterest.com/oncotarget/ Reddit - www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
In a trending paper published by Oncotarget on March 2, 2021, researchers conducted a study to better understand why young Andean people are disproportionately affected by hepatocellular carcinoma (HCC) than others around the world.
Hepatocellular carcinoma (HCC) is one of the most heterogeneous forms of cancer, and affects older patients commonly after they have had prolonged liver disease. However, among Andean people, half of the total patients who develop HCC are adolescents and young adults. Researchers—from Sorbonne Université, Institut Pasteur, Université de Rennes, and Université de Toulouse in France, and the Instituto Nacional de Enfermedades Neoplásicas in Peru—conducted a study to better understand HCC in Andean people.
“To deepen our understanding of the molecular determinants of the disease in this population, we conducted an integrative analysis of gene expression and DNA methylation in HCC developed by 74 Peruvian patients, including 39 adolescents and young adults.” Read the full study: https://www.oncotarget.com/article/27890/text/
The Trending with Impact series highlights Oncotarget publications attracting higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. More from Trending with Impact: https://www.oncotarget.org/tag/trending-with-impact/
About Oncotarget:
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit www.oncotarget.com or follow us:
SoundCloud - @oncotarget Facebook - www.facebook.com/Oncotarget/ Twitter - twitter.com/oncotarget LinkedIn - www.linkedin.com/company/oncotarget Instagram - www.instagram.com/oncotargetjrnl/ YouTube - www.youtube.com/OncotargetYouTube Pinterest - www.pinterest.com/oncotarget/ Reddit - www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Oncotarget published this top-performing paper in 2018, when researchers compared the overall survival, average total healthcare costs, and resource utilization among patients with advanced cancers who received either standard care or precision, targeted oncology.
The researchers, from Intermountain Healthcare facilities (located in Utah and California, U.S.) and California’s Stanford University School of Medicine, conducted a well-read study published in 2018, titled: “Precision oncology in advanced cancer patients improves overall survival with lower weekly healthcare costs.” This paper currently presents with an Altmetric attention score of 484. Read about the study: https://www.oncotarget.com/article/24384/text/ Top Oncotarget publications rated by Altmetric Attention Score: https://www.oncotarget.com/news/altmetric/
The Top-Performer series highlights research literature published in Oncotarget that has generated a high Altmetric score. Altmetric scores, located at the top-left of trending Oncotarget papers, provide an at-a-glance indication of the volume and type of online attention the research has received. More from the Top-Performer series: https://www.oncotarget.org/tag/top-performer/
About Oncotarget:
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit www.oncotarget.com or follow us:
SoundCloud - @oncotarget Facebook - www.facebook.com/Oncotarget/ Twitter - twitter.com/oncotarget LinkedIn - www.linkedin.com/company/oncotarget Instagram - www.instagram.com/oncotargetjrnl/ YouTube - www.youtube.com/OncotargetYouTube Pinterest - www.pinterest.com/oncotarget/ Reddit - www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
In February, 2021, researchers from Spain conducted a study published in Oncotarget, titled: “Head to head evaluation of second generation ALK inhibitors brigatinib and alectinib as first-line treatment for ALK+ NSCLC using an in silico systems biology-based approach.”
This trending paper was authored by researchers practicing at the Hospital Germans Trias i Pujol, Takeda Farmacéutica España, Anaxomics Biotech, and Universitat Pompeu Fabra.
The researchers used a computer simulated modeling system to highlight the strengths and weaknesses of two ALK inhibitors. They first began their study by characterizing the pathophysiology of ALK+ NSCLC after completing a detailed review of review papers published in PubMed between 2013 and 2018. Read the full study here: https://www.oncotarget.com/article/27875/text/
The Trending with Impact series highlights Oncotarget publications attracting higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. More from Trending with Impact: www.oncotarget.org/tag/trending-with-impact/
About Oncotarget:
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit www.oncotarget.com or follow us:
SoundCloud - @oncotarget Facebook - www.facebook.com/Oncotarget/ Twitter - twitter.com/oncotarget LinkedIn - www.linkedin.com/company/oncotarget Instagram - www.instagram.com/oncotargetjrnl/ YouTube - www.youtube.com/OncotargetYouTube Pinterest - www.pinterest.com/oncotarget/ Reddit - www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
In the cover paper of this week's issue of Oncotarget, titled: "The cancer testis antigens CABYR-a/b and CABYR-c are expressed in a subset of colorectal cancers and hold promise as targets for specific immunotherapy," researchers evaluate CABYR isoforms a/b and c mRNA expression in colorectal cancer in hopes of determining whether or not these proteins may be promising vaccine targets. Read the full study here: https://doi.org/10.18632/oncotarget.27897 Oncotarget Volume 12, Issue 5: https://www.oncotarget.com/archive/v12/i5/
About Oncotarget:
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit www.oncotarget.com or follow us:
SoundCloud - @oncotarget Facebook - www.facebook.com/Oncotarget/ Twitter - twitter.com/oncotarget LinkedIn - www.linkedin.com/company/oncotarget Instagram - www.instagram.com/oncotargetjrnl/ YouTube - www.youtube.com/OncotargetYouTube Pinterest - www.pinterest.com/oncotarget/ Reddit - www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Listen to short summaries of the latest oncology-focused research literature published in this week's issue of Oncotarget Volume 12, Issue 5. Click here for the complete issue: https://www.oncotarget.com/archive/v12/i5/
Oncotarget Volume 12, Issue 5 features:
Cover Paper: "The cancer testis antigens CABYR-a/b and CABYR-c are expressed in a subset of colorectal cancers and hold promise as targets for specific immunotherapy." https://doi.org/10.18632/oncotarget.27897
Research Perspective: "Tumor mutational burden as a predictor of immunotherapy response in breast cancer." https://doi.org/10.18632/oncotarget.27877
Research Paper: "STAT3 induces the expression of GLI1 in chronic lymphocytic leukemia cells." https://doi.org/10.18632/oncotarget.27884
Research Paper: "Multi-modal effects of 1B3, a novel synthetic miR-193a-3p mimic, support strong potential for therapeutic intervention in oncology." https://doi.org/10.18632/oncotarget.27894
Research Paper: "Mutational profile of skin lesions in hepatocellular carcinoma patients under tyrosine kinase inhibition: a repercussion of a wide-spectrum activity." https://doi.org/10.18632/oncotarget.27891
Research Paper: "Development of a ghrelin receptor inverse agonist for positron emission tomography." https://doi.org/10.18632/oncotarget.27895
Research Paper: "Global DNA hypermethylation pattern and unique gene expression signature in liver cancer from patients with Indigenous American ancestry." https://doi.org/10.18632/oncotarget.27890
Research Paper: "Fine–mapping of two differentiated thyroid carcinoma susceptibility loci at 2q35 and 8p12 in Europeans, Melanesians and Polynesians." https://doi.org/10.18632/oncotarget.27888
Research Paper: "Quantitative proteome profiling stratifies fibroepithelial lesions of the breast." https://doi.org/10.18632/oncotarget.27889
About Oncotarget:
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit www.oncotarget.com or follow us:
SoundCloud - @oncotarget Facebook - www.facebook.com/Oncotarget/ Twitter - twitter.com/oncotarget LinkedIn - www.linkedin.com/company/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube Pinterest - www.pinterest.com/oncotarget/ Reddit - www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
A review paper published this month in Oncotarget by researchers from the University of Modena and Reggio Emilia in Italy and the Sulaiman AlRajhi Medical School in Saudi Arabia is trending, and titled, “Cancer stem cells and macrophages: molecular connections and future perspectives against cancer.” (Read the paper here: https://www.oncotarget.com/article/27870/text/)
Two authors of this review paper, Dr. Beatrice Aramini and Dr. Valentina Masciale, provide an overview of their research on the complex crosstalk between cancer stem cells and macrophages, and potential anti-cancer strategies for future studies.
The Trending with Impact series highlights Oncotarget publications attracting higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. (More from Trending with Impact: https://www.oncotarget.org/tag/trending-with-impact/)
About Oncotarget:
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit www.oncotarget.com or connect with us on:
SoundCloud - @oncotarget Facebook - www.facebook.com/Oncotarget/ Twitter - twitter.com/oncotarget LinkedIn - www.linkedin.com/company/oncotarget Pinterest - www.pinterest.com/oncotarget/ Reddit - www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Hundreds of scientific studies, reviews, and analyses are being published from around the world at any given time. This can make reading the latest research literature a time consuming task—depending, of course, on the quantity of papers one hopes to consume. As a tool to help alleviate this important undertaking, many researchers have taken to listening to one of the top open-access podcasts of 2020 and 2021: The Oncotarget Podcast.
After a paper is published, it is added to an enhanced post-publication service provided by Oncotarget, in an effort to help authors reach a wider audience. This podcast series is another way to widely distribute the research that is published with free access by Oncotarget. Oncotarget Podcast episodes regularly include audio readings, press releases, and interviews with authors about their latest and trending papers published by Oncotarget. Player.fm (https://player.fm/podcasts/open-access) rated the Oncotarget Podcast on their lists of Best Open Access Podcasts of 2020 and 2021.
Oncotarget, and Impact Journals as a whole, is constantly expanding the definition of open-access to include a wide variety of accessibility-based audio and visual media to support researchers and readers with disabilities. Creators of the Oncotarget Podcast hope that offering audible renderings of literature from Oncotarget.com, and of blog posts from Oncotarget.org and Oncotarget.net, will be helpful for the vision impaired community.
Stay up-to-date with all of the latest oncology-focused research literature published by Oncotarget by subscribing to the Oncotarget Podcast, which can be found on Soundcloud, Apple, Stitcher, and Blubrry podcast streaming services.
About Oncotarget:
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit www.oncotarget.com or connect with:
SoundCloud - @oncotarget Facebook - www.facebook.com/Oncotarget/ Twitter - twitter.com/oncotarget LinkedIn - www.linkedin.com/company/oncotarget Pinterest - www.pinterest.com/oncotarget/ Reddit - www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Dr. Mikhail V. Blagosklonny, M.D., Ph.D., Editor-in-Chief of Oncotarget, and Professor, at Roswell Park Cancer Institute, published "The goal of geroscience is life extension" which was selected as the Featured Cover Paper for Volume 12 Issue 3 and reported that although numerous drugs seemingly extend healthspan in mice, only a few extend lifespan in mice and only one does it consistently. Some of them, alone or in combination, can be used in humans, without further clinical trials.
Dr. Mikhail V. Blagosklonny from The Roswell Park Cancer Institute said, "Although we do not know everything about aging, we now know enough to start its pharmacologic suppression using clinically approved drugs."
Published in 2010, these opening words of the paper entitled "Increasing healthy lifespan by suppressing aging in our lifetime: preliminary proposal" are still relevant today.
Hyperfunction of these signaling pathways directly drive all age-related diseases, which are manifestations of aging. We just need clinically available inhibitors of these signaling pathways to extend both healthspan and lifespan, by slowing aging.
A mere extension of healthspan is not enough: drugs that fail to extend lifespan in mice will fail to extend lifespan in humans, if used as a monotherapy.
Yet, in rational combinations with life-extending drugs, "healthspan-only" drugs may extend lifespan further.
In this Oncotarget publication, Dr. Blagosklonny reviews drugs that extend lifespan and healthspan in mammals, in contrast to those that may affect only healthspan without lifespan, and discusses how to proceed with clinical application of lifespan-extending drugs.
Blagosklonny concluded in their Oncotarget Research Perspective, "If we want to live longer, we have no choice, but to use drugs such as rapamycin, which extends life in short-lived mammals and is approved for humans use. After all, humans are mammals, and there is no reason to think that they will not work in humans."
Please note: This review is intended for a professional audience. This article does not represent medical advice or recommendations to patients. The media should exercise caution and seek expert medical advice for interpretation, when referring to this article. Medical doctors interested in this topic may e-mail the author at Blagosklonny@rapalogs.com or follow on Twitter @Blagosklonny
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27882
Full text - https://www.oncotarget.com/article/27882/text/
Correspondence to - Mikhail V. Blagosklonny - Blagosklonny@oncotarget.com, Blagosklonny@rapalogs.com
Keywords - aging, longevity, rapamycin, mTOR, metformin
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
The cover for issue 2 of Oncotarget features Figure 4, "Combination therapy TA99/ICB reduced the lung tumor burden in the B16 model of metastases," published in "Improved therapeutic efficacy of unmodified anti-tumor antibodies by immune checkpoint blockade and kinase targeted therapy in mouse models of melanoma" by Pérez-Lorenzo, et al. which reported that here, the authors showed that removing immune suppression and enhancing stimulatory signals increased the anti-tumor activity of unmodified TA99 antibodies with a significant reduction of growth of solid tumors and lung metastases in mouse models of melanoma.
Immune checkpoint blockade enhanced the efficacy of TA99, which was associated with greater CD8 /Foxp3 , NK1.1 and dendritic cell infiltrates, suggestive of an increased anti-tumor innate and adaptive immune responses.
Moreover, they found an improved therapeutic effect when YUMM tumor-bearing mice were treated with TA99 combined with MEKi and immune checkpoint blockade.
The Oncotarget findings suggest that MEKi induced an increased expression of tumor-associated antigens, which in combination with anti-tumor antibodies, generated a robust adaptive anti-tumor response that was sustained by immune checkpoint inhibition therapy.
The authors postulate that combining anti-tumor antibodies with standard-of-care strategies such as immune checkpoint blockade or targeted therapy, will improve therapeutic outcomes in cancer.
Dr. Angela M. Christiano from The Columbia University said, "It is well accepted that tumor development and progression is usually controlled by immunosurveillance mechanisms in which specific and non-specific immunological responses are constantly mounted against tumor cells."
Passive administration of anti-tumor antibodies generally functions by targeting malignant cells through IgG-mediated antibody-dependent cellular cytotoxicity, which is a rapid but relatively short-acting anti-tumor response.
Alternatively, they and others also demonstrated that the administration of anti-tumor antibodies induces long-lasting FcR-dependent tumor specific immunity in the host, with kinetics consistent with an induced adaptive immune response against the tumor.
In this model, anti-tumor antibodies, alone or in combination with chemotherapy, will promote innate cell-mediated ADCC, and the capture and processing of antigens by antigen presenting cells, with the subsequent stimulation and homing of antigen-specific effector T lymphocytes to the tumor site, leading to tumor elimination, a phenomenon the researchers and others referred to as the “vaccinal effect”.
With the use of the B16 and YUMM mouse models of melanoma and the anti-TYRP1 mouse monoclonal antibody TA99, we demonstrated that the therapeutic effects of these unmodified anti-tumor antibodies can be enhanced by ICB through the stimulation of both innate and adaptive anti-tumor immune responses.
In addition, they found that the MEK inhibitor -induced increased expression of melanosomal antigens further enhanced the anti-melanoma response to combination therapy with anti-tumor antibodies and immune checkpoint blockade in mouse models of melanoma.
The Christiano Research Team concluded in their Oncotarget Research Paper, "Together with our preclinical data, these results invite further clinical investigation of unmodified anti-tumor antibodies in combination with ICB and targeted therapies, and may represent promising and innovative therapeutic interventions for the successful management of patients with advanced melanoma and other cancers."
Full text - https://www.oncotarget.com/article/27868/text/
Correspondence to - Angela M. Christiano - amc65@cumc.columbia.edu
Keywords - anti-tumor antibodies, targeted therapy, immunotherapy, combination therapies, melanoma
Volume 11, Issue 28 of Oncotarget features "Genetic analysis of the cooperative tumorigenic effects of targeted deletions of tumor suppressors Rb1, Trp53, Men1, and Pten in neuroendocrine tumors in mice" by Xu et, al. which reported that the authors examined whether the TSGs Rb1, Trp53, Pten, and Men1 have cooperative effects in suppressing neuroendocrine tumors in mice.
By monitoring growth and examining the histopathology of the pituitary and pancreas in these mice, the authors demonstrated that pRB had the strongest cooperative function with PTEN in suppressing Pit NETs and had strong cooperative function with Menin and TRP53, respectively, in suppressing Pit NETs and Pan NETs. TRP53 had weak cooperative function with PTEN in suppressing pituitary lesions.
Collectively, the data indicated that pRB and PTEN pathways play significant roles in suppressing Pit NETs, while the Menin-mediated pathway plays a significant role in suppressing Pan NETs. Understanding the molecular mechanisms of these genes and pathways on NETs will help us understand the molecular mechanisms of neuroendocrine tumorigenesis and develop effective preclinical murine models for NET therapeutics to improve clinical outcomes in humans.
Dr. Eugenia Y. Xu from Rutgers and Princeton University as well as Dr. Daniel A. Notterman from Princeton University said, "Human pituitary neuroendocrine tumors (PitNETs) are the third most common intracranial neoplasms and represent approximately 10–25% of all primary intracranial tumors."
Additionally, in rare cases, RB1 has been found with epigenetic mutations in the promoter region in Pit NETs suggesting that inactivation of the RB pathway contributes to the development of Pit NETs. Compound mice with concomitant deletions of Men1 and Pten develop Pit NETs and Pan NETs and mice with p18–/– Pten+/– mutations develop Pit NETs, suggesting that PTEN plays a role in pituitary and pancreatic islet tumorigenesis.
However, Men1 deletion mice develop pars distalis prolactinomas and Rb1 deletion mice develop pars intermedia tumors of the pituitary, suggesting that the functions of Menin and pRB may not fully overlap.
Here they investigate the question of whether Men1 and Rb1 have cooperative tumorigenic effects on NETs using tissue-specific double homozygous deletions of Men1 and Rb1 in mice.
The Oncotarget authors report that the characterization of Pit NETs and Pan NETs with double homozygous deletions of TSGs and illustrate that pRB has the strongest cooperative function with PTEN in suppressing Pit NETs and has a strong cooperative function with Menin and TRP53, respectively, in suppressing Pit NETs and Pan NETs in mice.
The Xu/Notterman Research Team concluded in their Oncotarget Research Paper, "our data clearly demonstrate that TSGs Rb1, Pten, Men1, and Trp53 have distinct tissue specificity in neuroendocrine tumorigenesis in mouse and likely in man. The mouse models here and deletion of these TSGs in MIP-Cre mice will help further our understanding the molecular function of these TSGs and their pathways in PitNET and PanNET pathogenesis, which will help develop targeted novel therapeutic options in treating human patients."
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27660
Full text - https://www.oncotarget.com/article/27660/text/
Correspondence to - Eugenia Y. Xu - exu@princeton.edu and Daniel A. Notterman - dan1@princeton.edu
Keywords - neuroendocrine tumors, RB1, Trp53, PTEN, Men1
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
Volume 11, Issue 28 of Oncotarget features "Rapid onset type 1 diabetes with anti-PD-1 directed therapy", by Yun et al. and reported that Type 1 diabetes is a rare immune-related adverse event caused by checkpoint inhibitors with serious risk for diabetic ketoacidosis.
Of the patients who received immunotherapy, 5 patients were found to have type 1 diabetes, all of whom presented with DKA requiring insulin at 20 to 972 days from their first anti-PD- 1 dose.
Four patients had new-onset diabetes with mean Hb A1c of 9.1% on DKA presentation and persistent elevations over time.
Two patients who tested positive for glutamic acid decarboxylase antibodies presented with DKA at 20 and 106 days from first anti-PD-1 administration whereas patients who were autoantibody negative had DKA more than a year later.
The case series suggests that monitoring glycemia in patients on PD-1 inhibitors is not predictive for diabetes occurrence.
Dr. Sandip Pravin Patel from The Division of Hematology-Oncology in the Department of Medicine at The University of California San Diego said, "Cancer immunotherapy has broadened in clinical use over the last decade with FDA approval for treatment of various malignancies including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma, urothelial carcinoma, head, and neck carcinomas, cutaneous squamous cell cancer, microsatellite unstable tumors, and Hodgkin's lymphoma."
Autoimmune type 1 diabetes is generally associated with positive autoantibodies to islet proteins including glutamic acid decarboxylase, insulin, insulinoma-associated antigen-2, zinc transporter 8, and islet cells.
However, only a subset of patients who acquire type 1 diabetes is found to have autoantibodies and specific HLA alleles, making these biomarkers poor predictors of diabetes incidence.
Given the rarity of type 1 diabetes as an ir AE, the authors sought to characterize the real-world diagnosis, management, and sequelae of patients who developed this ir AE in the context of their immune checkpoint blockade.
This Oncotarget paper highlights the rapid kinetics of type 1 diabetes in patients on checkpoint inhibitors.
Type 1 diabetes presented as DKA for all patients in this series and all but one patient had a new diagnosis of diabetes, without antecedent laboratory or imaging findings.
The Patel Research Team concluded in their Oncotarget Research Paper that their case series illustrates the rare incidence of immunotherapy-induced type 1 diabetes and describes the rapid course of this disease in patients.
Regardless of whether or not patients remain on checkpoint inhibitors, those with immunotherapy-induced diabetes are at risk for hyperglycemia and recurrent DKA. Surveillance of glycemia or Hb A1c does not predict diabetes but does have a role after type 1 diabetes arises as glycemia fluctuates and elevated Hb A1c levels persist.
Furthermore, GAD antibodies are present in about half of patients who develop type 1 diabetes after immunotherapy, warranting additional investigations into whether this is all association and a marker of immune attack.
Given the absence of prescient laboratory or imaging findings in patients who develop type 1 diabetes on anti-PD-1 therapy, patients should be counseled on the symptoms of hyperglycemia which include polyuria, polydipsia, abdominal pain, nausea and emesis and seek medical attention immediately.
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27665
Full text - https://www.oncotarget.com/article/27665/text/
Correspondence to - Sandip Pravin Patel - patel@ucsd.edu
Keywords - type 1 diabetes, diabetic ketoacidosis (DKA), immune-related adverse event (irAE), immunotherapy, PD-1 inhibitors
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
The cover for issue 28 of Oncotarget features Figure 5, "TMEM165 expression levels alters N-linked glycosylation," by Murali, et al., and reported that the TMEM165 protein was not detected in non-malignant matched breast tissues and was detected in invasive ductal breast carcinoma tissues by mass spectrometry.
The hypothesis is that the TMEM165 protein confers a growth advantage to breast cancer.
The authors created a CRISPR/Cas9 knockout of TMEM165 in the human invasive breast cancer cell line MDAMB231.
Furthermore, they find that TMEM165 expression alters the glycosylation of breast cancer cells and these changes promote the invasion and growth of breast cancer by altering the expression levels of key glycoproteins involved in the regulation of the epithelial to mesenchymal transition such as E-cadherin.
These studies illustrate new potential functions for this Golgi membrane protein in the control of breast cancer growth and invasion.
Dr. Karen L. Abbott from The University of Oklahoma Health Sciences Center, Department of Biochemistry and Molecular Biology said "Breast cancer is the most commonly diagnosed cancer in women."
The TMEM165 protein was identified by mass spectrometry in invasive breast carcinoma tissue with no detection in patient-matched adjacent normal breast tissues.
The authors analyzed TCGA breast cancer cases to examine TMEM165 expression levels in all molecular types of human breast cancer using UALCAN.
They found that TMEM165 is amplified across all types of breast cancer compared to normal breast tissue with IDC cases having the highest levels of TMEM165 expression.
In the present study, the authors report that TMEM165 is upregulated in human breast cancer cell lines and patient tumor tissues and increased expression of TMEM165 correlates with poor prognosis in breast cancer patients.
Collectively, the data demonstrate that overexpression of TMEM165 promotes EMT in breast cancer suggesting a novel role for TMEM165 as a driver of tumor invasion making it a prognostic marker and potential therapeutic target for breast cancer.
The Abbott Research Team concluded in their Oncotarget Research Paper, "we have expanded on our initial 2012 glycoproteomic study that was the first to identify TMEM165 protein as a potential biomarker for breast carcinoma. In this study, we have provided initial mechanistic studies that indicate that TMEM165 expression drives the growth and invasion of breast cancer. TMEM165 expression levels could be a potential prognostic marker for predicting DCIS cases that may progress to invasive disease. Larger prospective cohorts will need to be analyzed to determine the link between TMEM165 levels and the progression to IDC. We find that IDC patients with higher TMEM165 expression levels have reduced overall survival making this protein a target for the development of new therapeutic strategies to limit the progression of breast cancer."
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27668
Full text - https://www.oncotarget.com/article/27668/text/
Correspondence to - Karen L. Abbott - Karen-Abbott@ouhsc.edu
Keywords - TMEM165, migration, invasion, breast cancer, glycosylation
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
The cover for issue 49 of Oncotarget features Figure 4, "CART-Tree analysis for overall survival in IMDC intermediate risk group," by Guida, et al.recently published in "Identification of international metastatic renal cell carcinoma database consortium (IMDC) intermediate-risk subgroups in patients with metastatic clear-cell renal cell carcinoma" which reported that as these patients have different prognosis, the aim of this study is to better characterize IR patients in order to better tailor the treatment.
A multivariable Cox model with backward selection procedure and a Classification and Regression Tree analysis were performed to identify which prognostic factors were associated to OS in IR patients.
Median OS for patients with PLT > UNL was 18 months versus 29 months for patients with normal PLT count.
The selection of PLT count was confirmed on bootstrap samples and was also selected for the first split of the CART-tree analysis.
Elevated PLT count seems to identify a subgroup of patients with poor outcome in the IMDC intermediate-risk population with ccRCC.
Dr. Laurence Albiges from The Université Paris-Saclay said, "The risk stratification models for metastatic renal cell carcinoma (mRCC) patients were developed as clinical tool to guide counseling, to predict individual patient prognosis and also to design clinical trial."
Patients lacking these negative factors have a good prognosis and may reach a longer survival; patients presenting 1 or 2 factors have an intermediate risk of death with a median overall survival about 23 months; patients with 3 or more factors have an expected poor risk outcome with median survival about 8 months.
Only in the poor risk group the decision-making algorithm was different: these patients were not candidate for upfront cytoreductive nephrectomy and in selected cases could benefit of mTOR inhibitor temsirolimus in first-line setting.
In the phase III trial Checkmate-214 nivolumab plus ipilimumab immunotherapy combination significantly prolonged OS versus sunitinib in intermediate and poor-risk untreated patients with mRCC.
The Albiges Research Team concluded in their Oncotarget Research Paper that given the rapidly evolving field of systemic treatment in mRCC, one of the most important challenges in mRCC is how prognostic stratification will guide front-line treatment selection.
Additionally characterization of heterogeneous IMDC intermediate-risk groups of patients should be seeked for optimal clinical trials design and stratification.
High platelet count reflecting the cancer-related inflammatory status and seems to segregate patients with the worst prognosis in the intermediate-risk group.
Further analyses are ongoing to validate these findings in patients receiving first line CPI based combination in first line.
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27762
Full text - https://www.oncotarget.com/article/27762/text/
Correspondence to - Laurence Albiges - Laurence.ALBIGES@gustaveroussy.fr
Keywords - metastatic clear-cell renal cell carcinoma, IDMC, intermediate-risk, heterogeneous prognostic, platelets
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
The cover for issue 45 of Oncotarget features Figure 3, "Representative images of whole tumor volume segmentation of the co-registered T1 post-contrast sequence and apparent diffusion coefficient (ADC) map, yielding the corresponding ADC histogram distribution utilized for data analysis," recently published in “Diffusion-weighted MR imaging histogram analysis in HIV positive and negative patients with primary central nervous system lymphoma as a predictor of outcome and tumor proliferation” by Khan, et al.
This authors reported that the aim of this study is to investigate the correlation between ADC parameters, Ki-67 expression, overall survival and progression free survival in PCNSL.
Selection criteria yielded 90 patients, 23 patients living with HIV and 67 immunocompetent patients.
In patients with available Ki-67 expression data, nADCmean, nADC15 and nADC75 inversely correlated with Ki-67 expression.
For PLWH, there was no correlation between ADC parameters and Ki-67 expression or clinical outcomes.
ADC histogram analysis can predict tumor proliferation and survival in immunocompetent patients with PCNSL, but with limited utility in PLWH.
Dr. Bilal Khan from The Baylor College of Medicine said, "Primary central nervous system lymphoma (PCNSL) is a rare subgroup of non-Hodgkin lymphoma confined to the central nervous system, with more than 90% of cases classified as Diffuse Large B-cell Lymphoma."
Diffusion weighted imaging and corresponding apparent diffusion coefficient maps can provide a representation of the cellular microenvironment with several studies demonstrating that ADC values can predict tumor cellularity across various neoplasms, including lymphomas.
In a recent similar study of whole tumor histogram analysis in PCNSL performed by the authors of this study, multiple ADC parameters were inversely correlated with Ki-67 expression and associated with poorer OS.
However, tumor segmentation was performed using only the ADC sequence with the potential inclusion of intra-tumoral necrosis, hemorrhage or regions outside of the actual solid tumor that would otherwise have been excluded with contrast co-registration, ultimately providing a suboptimal representation of true tumor parenchyma.
The primary aim of this study is to more comprehensively evaluate the relationship between ADC calculations with tumor Ki-67 expression and clinical outcomes using a larger patient sample with the inclusion of PLWH and whole tumor segmentation with T1 post contrast co-registration.
The Oncotarget author's hypothesis is that ADC values will inversely correlate with Ki-67 expression and that tumors with higher ADC values above the median will have improved OS and PFS.
The Khan Research Team concluded in their Oncotarget Research Paper that the role of MR in PCNSL historically has been the detection and qualitative evaluation of response to treatment.
DWI and derived ADC maps have been a well-established tool in neuroimaging, but the use of ADC histogram profiling has not been widely accepted in daily practice.
This data expands the role of conventional MR imaging by utilizing quantitative ADC histogram analysis to predict clinical outcomes and tumor expression of Ki-67, a biomarker for tumor proliferative activity, in immunocompetent PCNSL patients.
The role of using ADC as an imaging biomarker in PLWH may be limited.
Quantitative ADC histogram analysis should be strongly considered as part of the imaging protocol in the evaluation of immunocompetent patients with PCNSL.
DOI - https://doi.org/10.18632/oncotarget.27800
Full text - https://www.oncotarget.com/article/27800/text/
The cover for issue 44 of Oncotarget features Figure 1, "Schematic diagram of the human IGF2 gene structure," by Radhakrishnan, et al. recently published in "Methylation of a newly identified region of the INS-IGF2 gene determines IGF2 expression in breast cancer tumors and in breast cancer cells" which reported that these authors previously demonstrated that IGF2 protein levels are higher in BC tissues from African American women than in Caucasian women.
They also showed that high IGF2 protein levels are expressed in normal breast tissues of African American women while little or no IGF2 was detected in tissues from Caucasian women.
Thus, they designed this study to determine if differentially methylated regions of the IGF2 gene correspond to IGF2 protein expression in paired breast tissues and in BC cell lines.
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.
Since IGF2 promotes metastasis and chemoresistance, we propose that IGF2 levels contribute to BC aggressiveness.
Dr. Daisy D. De León from The Loma Linda University School of Medicine said, "Insulin-Like Growth factor 2 (IGF2) is a fetal growth factor that plays a critical function in fetal differentiation and metabolism by signaling through the IGF-I receptor and the insulin receptor."
Thus, IGF2 expression is important in normal breast development and increased IGF2 expression in the mammary gland contributes to BC malignancy.
This gene is located on the short arm of chromosome 11 at position 15.5. Methylation of the IGF2 gene regulatory regions occurs during the formation of an egg or sperm cell, and it is distinct and differentially modified depending on the parental origin of the allele.
In particular, dysregulation in the methylation of the IGF2 gene promoters occurs in several cancers including BC and this altered methylation leads to different clinical features in BC disease.
In spite of these advances, there is currently no consensus regarding the methylation status of the IGF2 gene, and its relationship to the levels of IGF2 protein expressed in normal breast or in breast cancer tissues.
DNA methylation patterns of the IGF2 gene were also analyzed in several BC cell lines to determine if there was a correlation between methylation of the IGF2 gene regulatory regions and the cellular expression levels of IGF2 protein.
The De León Research Team concluded in their Oncotarget Research Paper, "the present study shows that IGF2 expression in BC cells and in paired Normal- Malignant breast tissues are determined by the methylation of a novel region in the INS-IGF2 locus. We are currently studying the mechanisms underlying the methylation of the INS-IGF2 and how they control IGF2 expression. Upregulation of IGF2 in terms of the methylation patterns of the DVDMR may have an important function in the tumorigenesis of the breast. In conclusion, we propose that the INS-IGF2 DVDMR may be a useful tool to identify women at risk of developing a more aggressive BC disease."
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27655
Full text - https://www.oncotarget.com/article/27655/text/
Correspondence to - Daisy D. De León - ddeleon@llu.edu
Keywords - IGF2, INS-IGF2, hypermethylation, DMR, epigenetics
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget recently published "CD44+/EPCAM+ cells detect a subpopulation of ALDHhigh cells in human non-small cell lung cancer: A chance for targeting cancer stem cells?" which reported that a comparison between ALDH high cells and CD44 cells have been previously described with no significant correlation.
This cross-sectional study analyzed the expression of ALDHhigh/low cells and the positivity for CD44 and epithelium cell adhesion molecule antigens in surgical lung cancer tissues.
There was a highly positive correlation between the expressions of ALDHhigh and CD44 /EPCAM cells, with a Pearson’s correlation coefficient equal to 0.69, and Spearman’s correlation coefficient equal to 0.52.
The average paired difference between the expression of ALDHhigh and CD44 /EPCAM cells was very close to 0, being 0.1%; there was no difference between these subpopulations in terms of means.
The Oncotarget author’s study is the first attempt that identifies a high correlation between the ALDHhigh and the CD44 /EPCAM cells, thus suggesting the possibility to use this superficial marker for future target treatments against lung cancer stem cells.
Dr. Beatrice Aramini from The University of Modena and Reggio Emilia said, "The cancer stem cell (CSC) model was proposed over 30 years ago [1] and is a very important field of study in cancer research."
As a cancer stem cell marker in a panel of 11 non-small-cell lung cancer tumor samples, 45 NSCLC lines, and 7 small-cell lung cancer lines.
In 2013 a panel of lung cancer cell lines from primary tumors and characterized a small subpopulation as strongly positive for CD44, with the main population being weakly positive or negative for CD44. The co-expression of CD90 further narrowed down the putative stem cell population.
This showed the putative lung CSC phenotypes of CD166 /CD44 and CD166 /EPCAM with multipotent characteristics of stem cells in lung adenocarcinoma cells.
Hence, a triple-positive marker, EPCAM /CD166 /CD44, has recently been described in the human non-small cell lung cancer cell line.
Nevertheless, although ALDH is considered an intracellular enzyme and is the most used marker to identify CSCs in lung cancer, the scientific community has never correlated this intracellular marker with an epithelial marker, which may be very useful for targeting lung cancer stem cells.
The Aramini Research Team concluded in their Oncotarget Research Paper, “even if we hypothesized that the percentage of CD44 /EPCAM in ALDHhigh cell population would be less than 50% in other patients, the similarity of an intracellular marker highlighting ALDHhigh cell population with a superficial marker CD44 /EPCAM is a very important concept in terms of target treatment.
In summary, our research is an important starting point for further studies that are needed to better define the CD44 /EPCAM superficial marker highlighting lung cancer stem cells.”
Full text - https://www.oncotarget.com/article/27568/text/
The cover for Issue 42 of Oncotarget features Figure 4, "Generation of parametric and texture maps from radiofrequency data," recently published in "Quantitative ultrasound radiomics using texture derivatives in prediction of treatment response to neo-adjuvant chemotherapy for locally advanced breast cancer" by Dasgupta, et al. which reported that to investigate quantitative ultrasound based higher-order texture derivatives in predicting the response to neoadjuvant chemotherapy in patients with locally advanced breast cancer.
Three machine learning algorithms based on linear discriminant, k-nearest-neighbors, and support vector machine were used for developing radiomic models of response prediction.
The most helpful features in separating the two response groups were QUS-Tex1-Tex2 features.
The 5-year recurrence-free survival calculated for KNN predicted responders and non-responders using QUS-Tex1-Tex2 model was comparable to RFS for the actual response groups.
The Oncotarget authors report the first study demonstrating QUS texture-derivative methods in predicting NAC responses in LABC, which leads to better results compared to using texture features alone.
Dr. Gregory J. Czarnota from The Sunnybrook Health Sciences Centre, The University of Toronto, The Sunnybrook Research Institute, as well as York University said, "Breast cancer is the second most common cancer globally in terms of incidence, comprising 11.6% of all new cancers and is the 5th leading cause of mortality attributed to 6.6% of all cancer deaths."
Imaging modalities like ultrasonography, mammography, magnetic resonance imaging, and computed tomography are commonly used in response monitoring of NAC, which primarily considers long-term size related changes of the disease.
Radiofrequency data from QUS provides valuable information compared to conventional B-mode ultrasound imaging, where there is a loss of crucial details involved with instrument-based signal processing. The analysis of the power spectra from ultrasound RF data can be used to determine quantitative parameters, which include average scatterer diameter, average acoustic concentration, mid-band fit, spectral slope, spectral 0-MHz intercept.
The spatial distribution of features within QUS parametric images can be further studied using grey-level co-occurrence matrix analyses, which represent the angular relationship and distance between neighboring pixels.
In the study here, higher-order imaging features in the form of QUS texture-derivatives have been determined from pretreatment QUS data for patients with LABC undergoing NAC to predict treatment response.
The Czarnota Research Team concluded in their Oncotarget Research paper that QUS is a simple, easily accessible imaging modality, with similar scanning techniques akin to the B-mode US, which is widely used in clinical practice.
With appropriate data processing, it is possible to use the information normally processed to generate B-mode images to obtain additional information from tumors. These are related to tumor acoustic properties, which can be linked with biological features and clinical behavior. In this research, we established the role of higher-order imaging analysis (radiomics) of QUS in predicting treatment response to NAC involving 100 patients with LABC.
The work provides a framework for using QUS-radiomics in clinical practice to choose appropriate chemotherapy regimens or other treatment modalities like upfront surgery (in predicted chemo-resistant tumors), leading the way towards personalized oncology.
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27742
Full text - https://www.oncotarget.com/article/27742/text/
Correspondence to - Gregory J. Czarnota - gregory.czarnota@sunnybrook.ca
Keywords - radiomics, breast cancer, texture derivatives, quantitative ultrasound, neoadjuvant chemotherapy
The cover for Issue 41 of Oncotarget features Figure 7, "IPA ATM-signaling pathway in (A) EFV treated MRC-5 and (B) A549 cells," recently published in "Efavirenz induces DNA damage response pathway in lung cancer" by Marima, et al. which reported that the cell-cycle related genes are potential gene targets in understanding the effects of efavirenz in lung cancer.
The present study aimed at investigating the expression changes of cell-cycle related genes in response to EFV drug treatment in human non-small cell lung carcinoma and normal lung fibroblast cells.
The loss in nuclear integrity in response to EFV was detected by 4′, 6-diamidino-2-phenylindole staining. Gene expression profiling was performed using human cell cycle PathwayFinder RT2 Profiler™ PCR Array.
The expression changes of 84 genes key to the cell cycle pathway in humans following EFV treatment was examined.
Interestingly, the p53 signaling pathway was activated irrespective of the repressed ATM pathway in A549 cells as revealed by the Ingenuity Pathway Analysis.
Dr. Rahaba Marima from The University of Pretoria as well as The University of the Witwatersrand said, "The non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV) is frequently used in human immunodeficiency virus (HIV) treatment, and forms part of the first-line Highly Active Antiretroviral Treatment (HAART) treatment against HIV/AIDS."
Xulu and Hosie showed that ARV drugs including EFV caused apoptosis in the Human Squamous Cell carcinoma from Uterine Cervix cells and observed a change in morphological features such as rounding-up of cells, retraction of filopodia, blebbing and maintenance of plasma membrane integrity- characteristic features of apoptosis.
Due to the fact that the cell cycle is a tightly regulated process, eukaryotic cells respond to external stimuli such as DNA damage by activating signaling pathways that promote cell cycle arrest and DNA repair.
A previous study performed by the Marima Research group, involved assessing the effects of EFV on lung cancer cells at the cellular level on the physiological health of treated cells.
To date, several studies including Hecht et al., have revealed the cytotoxic effects of EFV against several cancer cells, but to our knowledge, no study yet has shown the anti-proliferative effects of EFV on lung epithelial cancer cells in relation to primary lung fibroblast cells.
In conjunction with preceding studies on EFV′s cyto-and-genotoxicity, this Oncotarget study is the first to reveal EFV mediated ATM/ATR genotoxicity in lung cells.
The Marima Research Team concluded in their Oncotarget Research Paper that the treatment of MRC-5 and A549 cells with EFV alters the gene expression of important factors that are essential in the maintenance of genomic stability in relation to the cell cycle.
This is particularly observed in the cancerous cells, with the significant down-regulation of AURKB and MAD2L2. Even though the normal p53 expression was shown here, p27, CASP3, Cyclin G1 and G2, NBN, RAD1 and RAD17 were significantly up-regulated.
Interestingly, the S-phase and DNA replication genes were downregulated; MCM4 in particular was –3.65 significantly down-regulated.
Depending on the severity of these effects in the physiological health of normal cells, EFV poses as a promising drug that can be used in synergy with chemo/radiotherapy.
Posttranscriptional gene regulation targeted by EFV in lung cells would also be interesting to pursue.
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27725
Full text - https://www.oncotarget.com/article/27725/text/
Correspondence to - Rahaba Marima - rahaba.marima@up.ac.za
Keywords - efavirenz, cell cycle, differential gene expression, DNA damage response pathway, lung cancer
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open-access biomedical journal covering research on all aspects of oncology.
The cover for issue 40 of Oncotarget features Figure 5, "miR-210 silences the proapoptosis member CASP8AP2," by Kling, et al. which reported that hypoxic Ewing's sarcoma cells release exosomes that promote sphere formation, a stem-like phenotype, in EWS cells by enhancing survival.
Analysis of the hypoxic exosomal miRNA cargo identified a HIF-1α regulated miRNA, miR-210, as a potential mediator of sphere formation in cells exposed to hypoxic exosomes.
The knockdown of HIF-1α in hypoxic EWS cells led to decreased exosomal miR-210 levels and reduced the capacity of hypoxic exosomes to form spheres.
Inhibition of miR-210 in hypoxic spheres attenuated sphere formation and overexpression of miR-210 in normoxic spheres significantly enhanced the number of EWS spheres.
Together, the findings in this Oncotarget study suggest that hypoxic exosomes promote stemness in EWS cells by delivering enriched miR-210 that is capable of down-regulating apoptotic pathways, resulting in the survival of cells with increased sphere formation.
Dr. Shantaram S. Joshi from The University of Nebraska Medical Center said, "Ewing's sarcoma (EWS) is an aggressive and highly malignant bone tumor that develops in children and adolescents."
HIF -1α has been demonstrated to regulate tumor formation and stem cell survival in hypoxic cancer cells by inhibiting apoptosis.
Emerging evidence indicates intercellular communication between tumor cells in hypoxic and normoxic regions contributes to functional differences associated with hypoxic tumors.
Other reports demonstrated that shCD99 EWS-derived exosomes could transfer enriched miR-34a to recipient EWS cells and stimulate neural differentiation while in another study, EWS-derived exosomes carrying EZH2 mRNA could be delivered intact to mesenchymal stem cells.
Studies in other cancer models investigating the role of hypoxic exosomes have provided insight into how hypoxic tumors can secrete exosomes that propagate an aggressive phenotype in cells outside the hypoxic niche.
Exosomes released from hypoxic prostate cancer cells enhanced sphere formation in normoxic cells, but the authors were unable to elucidate a mechanism describing how hypoxic exosomes promote stemness in normoxic cells.
The Joshi Research Team concluded in their Oncotarget Research Paper that this study describes a mechanism whereby EWS cells under hypoxic conditions release exosomes that enhance stemness in EWS cells.
The authors identified a hypoxia regulated miRNA significantly expressed in hypoxic cells and HypoxicEXO and characterized a potential target that facilitates an apoptotic pathway critical to sphere formation.
Ongoing studies are investigating the role of HIF-1α on regulating EWS stemness and together, the authors future aim is to investigate how HIF-1α selectively modulates the packaging of miRNAs into HypoxicEXO, and validate additional miRNAs that promote aggressive hypoxic phenotypes.
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27702
Full text - https://www.oncotarget.com/article/27702/text/
Correspondence to - Shantaram S. Joshi - ssjoshi@unmc.edu
Keywords - exosomes, hypoxia, Ewing's sarcoma, stemness, miR-210
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
The cover for issue 39 of Oncotarget features Figure 4, "Apoptosis assay of NRXN1-targeted ADC at IC50 dose calculated by growth inhibition curves," by Yotsumoto, et al. which reported that the authors identified transmembrane proteins overexpressed specifically in SCLC with little or no expression in normal tissues and decided to focus on the cell adhesion molecule neurexin-1.
The cell surface overexpression of NRXN1 was confirmed using flow cytometry in SCLC cell lines.
The combination of a primary anti-NRXN1 monoclonal antibody and a secondary ADC exhibited anti-tumor activity in SCLC cell lines.
Moreover, the knockout of NRXN1 in SHP77 cells resulted in a loss of the anti-tumor activity of NRXN1-mediated ADC therapy.
Thus, NRXN1 could be a novel target for ADC therapy for the treatment of SCLC that is worth further research.
Dr. Daiya Takai from The University of Tokyo Hospital and Dr. Takuma Yotsumoto from The University of Tokyo Graduate School of Medicine said, "Small cell lung cancer (SCLC) accounts for 10–15% of lung cancer, and its prognosis has remained relatively dismal for years."
Considering the high sensitivity of SCLC to chemotherapy, the selective delivery of a cytotoxic agent using ADC could be a novel treatment strategy for SCLC.
Five ADCs have been approved by The Food and Drug Administration:
Brentuximab vedotin for Hodgkin lymphoma Ado-trastuzumab emtansine for HER2-positive metastatic breast cancer Inotuzumab ozogamicin for acute lymphoblastic leukemia Gemtuzumab ozogamicin for CD33-positive acute myeloid leukemia, and Trastuzumab deruxtecan for unresectable or metastatic HER2-positive breast cancer patients who have received two or more prior anti-HER2-based regimens in a metastatic setting. In SCLC, DLL3, a cell surface Notch ligand that appears to be a direct downstream target of ASCL1, has been identified as a novel target for ADCs.
In this study, the Oncotarget authors aimed to identify novel molecular targets for ADCs in SCLC.
They herein report that NRXN1-mediated ADC exhibited anti-tumor activity in vitro, and thus NRXN1 could be a novel target of ADCs for SCLC.
The Takai/Yotsumoto Research Team concluded in their Oncotarget Research Paper "we identified NRXN1 as a new target for ADCs by screening membrane proteins using a computational-biological approach. The combination of the primary anti-NRXN1 monoclonal antibody and the secondary ADC exhibited anti-tumor activity in an NRXN1-expression dependent manner. NRXN1 could be a novel potential target of ADCs for SCLC that is worth further research."
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27718
Full text - https://www.oncotarget.com/article/27718/text/
Correspondence to - Daiya Takai - dtakai-ind@umin.ac.jps and Takuma Yotsumoto - tyotsumoto-ths@umin.ac.jp
Keywords - antibody-drug conjugates, small cell lung cancer, novel molecular targets, NRXN1, cell adhesion molecule
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
The cover for issue 38 of Oncotarget features Figure 3, "Summary of the time and cost for drug development (modified from DiMasi et al [2016]," by Katayama, et al. which reported that Pancreatic cancer is the most aggressive common cancer and is desperately in need of novel therapies.
In this study, the Oncotarget authors perform the first comprehensive analysis of the current clinical trial landscape in pancreatic cancer to better understand the pipeline of new therapies.
Studies were curated and categorized according to the phase of the study, the clinical stage of the study population, type of intervention under investigation, and biologic mechanism targeted by the therapy under study.
As of May 18, 2019, there were 430 total active therapeutic interventional trials testing 590 interventions.
The vast minority of trials are in phase III testing. 189 interventions are immunotherapies, 69 target cell signaling pathways, 154 target cell cycle or DNA biology, and 35 target metabolic pathways.
Dr. Jordan M. Winter from The Case Western Reserve University School of Medicine as well as The University Hospitals Seidman Cancer Center and Case Comprehensive Cancer Center said, "Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive of the common cancers."
The institute allocates roughly $6 billion annually to cancer research, and just over $100 million is dedicated to studying pancreatic cancer.
Other agencies and organizations like the Pancreatic Cancer Action Network, American Cancer Society, and the Department of Defense contribute significantly to this mission, likely adding more than $20 million per year in totality.
Along these lines, the authors have likely neared a survival ceiling for our patients in the absence of new discoveries that target other aspects of cancer biology, due to the additive toxicities of chemotherapeutic combinations.
Patients, family members, primary care providers, and oncologists battling together against pancreatic cancer often consider the same important questions: what new treatments are coming down the pike, and how soon will they arrive?
This work is necessary to better anticipate the timeframe for novel therapies against pancreatic cancer to reach the market. More importantly, this 20,000-foot view provides a foundation to discuss optimal resource allocation, with a principal goal to accelerate the pace of innovation, with an eye towards improving patient outcomes.
The Winter Research Team concluded in their Oncotarget Research Paper that the majority of PDAC trials are focused on immunotherapy, chemotherapy, and radiation.
Following the herd has not yet worked well for PDAC research; immunotherapy and precision therapy have yet to strongly impact this disease.
Finally, this compendium focuses on therapeutic studies and not early detection.
It is possible that the greatest advance in the future could be the discovery of an effective PDAC biomarker.
If the authors can detect PDAC at the PanIN 3 stage, therapeutic trials of invasive cancer become inconsequential.
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27727
Full text - https://www.oncotarget.com/article/27727/text/
Correspondence to - Jordan M. Winter - Jordan.Winter@UHhospitals.org
Keywords - pancreatic cancer, pancreatic ductal adenocarcinoma, clinical trial, novel treatment, drug development
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
The cover for issue 37 of Oncotarget features Figure 7, "The combination of romidepsin and KU60019 is synergistic in a xenograft model of MCL," by Scotto, et al. which reported that the antiproliferative effect induced by histone deactylase inhibitors is associated with the up-regulated expression of the cyclin-dependent kinase inhibitor p21. Paradoxically, the increased expression of p21 correlates with a reduced cell killing to the drug.
HDAC inhibitors appear to activate p21 expression via ataxia telangiectasia mutated activity.
The Oncotarget authors explored the potential synergistic interaction of the ATM inhibitor with romidepsin, given the potential complementary impact around p21. A synergistic cytotoxic effect was observed in all lymphoma cell lines examined when the HDACi was combined with KU60019. The increase in apoptosis correlates with decreased expression of p21 due to the ATM inhibitor.
KU60019 decreased expression of the cyclin-dependent kinase inhibitor at the transcriptional level, compromising the ability of HDACi to induce p21 and cell cycle arrest and ultimately facilitating a shift toward the apoptotic phase.
Central to the increased apoptosis observed when romidepsin is combined with KU60019 is the reduced expression of p21 and the absence of a G2/M cell cycle arrest that would be exploited by the tumor cells to evade the cytotoxic effect of the HDAC inhibitor.
Dr. Owen A. O'Connor from The Columbia University Medical Center said, "HDAC inhibitors (HDACi) have emerged as valuable drugs in the treatment of select lymphomas and synergize with a diverse range of pharmacological and biological agents."
The observation leads to the following hypothesis: if induction of p21 compromises the efficacy of HDAC inhibitors, then strategies to mitigate HDAC inhibitor induced p21 expression could lead to promising synergistic combinations.
Induction of p21 by HDAC inhibitors is compromised in A-T cells given that ATM activity is essential for HDAC inhibitor-induced p21 expression.
Collectively, these observations have led to the following hypothesis: If ATM activity is necessary for HDAC inhibitor mediated p21 induction, then selective ATM inhibitors could mitigate the HDAC induced p21 expression and potentiate its cytotoxic effect.
The ATM inhibitor nullifies HDAC induction of p21 expression resulting in a synergistic interaction.
KU60019 reduces p21 expression at the transcriptional level and antagonizes romidepsin transcriptional induction of p21. In both instances, the result is a markedly down-regulation of p21 expression at the protein level.
The O'Connor Research Team concluded in their Oncotarget Research Paper that it is intuitive that pleotropic drugs like HDACi are likely to have both favorable and unfavorable effects on cell growth and survival.
Strategies directed toward understanding how to mitigate the unfavorable influences of the class can lead to improved efficacy in rational combinations.
Many examples of drug synergy with HDAC inhibitors have been driven by random efforts in mixing and matching in order to identify possible complementary partners.
Obviously, a clear understanding of the molecular pharmacologic features of pleotropic drug classes like HDAC inhibitors can afford unique opportunities to think about logical combinations.
Ultimately, these approaches need to be translated to the clinic in order to establish therapeutic merit in the clinic.
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27723
Full text - https://www.oncotarget.com/article/27723/text/
Correspondence to - Owen A. O'Connor - owenaoconnor@gmail.com
Keywords - lymphoma, HDAC inhibitor, ATM inhibitor, p21, cell cycle
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com
The cover for issue 36 of Oncotarget features Figure 7, "Knockdown of APOBEC3B is associated with a lower tumor growth in an adrenocortical carcinoma xenograft mouse model," by Gara, et al. which reported that the role of APOBEC3B in adrenocortical carcinoma and the mechanisms through which its expression is regulated in cancer are not fully understood.
Here, the authors report that APOBEC3B is overexpressed in ACC and it regulates cell proliferation by inducing S phase arrest. They show high APOBEC3B expression is associated with a higher copy number gain/loss at chromosome 4 and 8 and TP53 mutation rate in ACC.
GATA3 was identified as a positive regulator of APOBEC3B expression and directly binds the APOBEC3B promoter region.
Both GATA3 and APOBEC3B expression levels were associated with patient survival.
This Oncotarget study provides novel insights into the function and regulation of APOBEC3B expression in addition to its known mutagenic ability.
Dr. Electron Kebebew from Stanford University said, "Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy."
The distinct pattern of DNA base alterations has been characterized in the cancer genome using high throughput deep sequencing technologies, that reflect the underlying mutational process.
Whole-genome and exome mutation analysis of The Cancer Genome Atlas data on multiple cancers has revealed that this pattern is consistent with the deaminase activity of the AID/APOBEC family of enzymes, therefore, implying its significance as an endogenous mutator and a crucial contributor to somatic mutations and genomic instability.
APOBEC3B is overexpressed in ovarian cancer cell lines and high-grade primary ovarian cancers.
In addition, APOBEC3B expression is positively correlated with the total mutation load, as well as, elevated levels of transversion mutations.
Given there are no well-established exogenous factors associated with ACC, the Oncotarget authors postulated whether APOBEC3B could be an endogenous mechanism of genomic instability/mutations in ACC and investigated its function in vitro and in vivo.
The Kebebew Research Team concluded in their Oncotarget Research Paper, "APOBEC3B overexpressed in ACC, and is associated with DNA damage, S phase arrest, higher copy number alterations and TP53 mutations in ACC. For the first time, we demonstrated that GATA3 directly regulates the expression of APOBEC3B and that both are prognostic markers in ACC."
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27703
Full text - https://www.oncotarget.com/article/27703/text/
Correspondence to - Electron Kebebew - kebebew@stanford.edu
Keywords - adrenocortical carcinoma, APOBEC3B, GATA3, prognosis, DNA damage
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
The cover for issue 26 of Oncotarget features Figure 8, "Proposed mechanism of action of ONC201," from Greer, et al.
TRAIL, a member of the TNF family of ligands, causes caspase–dependent apoptosis through activation of its receptors, death receptor 4 and DR5.
ONC201 was originally identified as a small molecule that inhibits both Akt and ERK, resulting in dephosphorylation of Foxo3a and thereby induces TRAIL transcription.
Recently, two independent groups, Wafik El Deiry at Fox Chase and Michael Andreeff at MD Anderson,reported that ONC201 induces cell death via cell stress mechanisms, independent of TRAIL transcription. Gene expression profiling analysis revealed that ONC201 induces endoplasmic reticulum (ER) stress or integrated stress response –related genes, such as Activating Transcription Factor 4 (ATF4) and C/EBP–homologous protein (CHOP).
The researchers in Dr. Lipkowitz's group at the Center for Cancer Research in the National Cancer Institute observed that ONC201 kills breast cancer cells via a TRAIL–independent mechanism. Time–lapse live cell imaging revealed that ONC201 induces cell membrane ballooning followed by rupture, distinct from the morphology of cells undergoing apoptosis. They found that ONC201 inhibits mitochondrial respiration and induces mitochondrial structural damage. Moreover, they found ONC201 reduces mitochondrial DNA copy number. Importantly, cells dependent on glycolysis, such as fumarate hydratase deficient cancer cells and multiple cancer cell lines with reduced amounts of mitochondrial DNA were resistant to ONC201. ONC201 induced ATF4 and CHOP in breast cancer cells, and the stress response it was partially dependent on the mitochondrial effects of ONC201.
"Our work identifies a novel mechanism of ONC201 cytotoxicity that is based on the disruption of mitochondrial function, leading to ATP depletion and cell death in cancer cells that are dependent on mitochondrial respiration. Our study also suggests that cancer cells that are dependent on glycolysis will be resistant to ONC201" Dr. Stanley Lipkowitz, Chief, Women's Malignancies Branch, NCI.
Full text – https://www.oncotarget.com/article/24...
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com/ or connect with @Oncotarget
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM
The cover for issue 31 of Oncotarget features Figure 4, "Concentration dose-response curves of sirolimus effect [55 nM–1 nM] on the number of cells per surviving colony in U2OS cell line after 2 weeks exposure," by Vasuri, et al. which reported that the authors evaluated the long-term effects of sirolimus on three different cell in vitro models, cultured in physiological conditions mimicking sirolimus-eluted stent, in order to clarify the effectiveness of sirolimus in blocking cell proliferation and survival.
Three cell lines were selected and growth in 10 ml of Minimum Essential Medium for 5 weeks with serial dilutions of sirolimus.
The number of colonies and the number of cells per colony were counted.
As a result, the number of WPMY-1 surviving colonies increased in a dose-dependent manner when treated with sirolimus, while the number of U2OS colonies progressively decreased.
In conclusion sirolimus showed the well-known cytostatic effect, but with an effect on clonogenic potential different among the different cell types.
Dr. Gianandrea Pasquinelli from The Bologna University said, "Rapamycin (sirolimus) is a widely used cytostatic drug blocking the cell cycle in the phase G1/S through the inhibition of the mammalian target of Rapamycin (mTOR) pathway, that has found several clinical applications, from immunosuppression in diabetes and organ transplantation to cancer therapy and drug-eluting stents (DES)"
Beside to its cytostatic activity, sirolimus was also discovered to protect normal human oral keratinocytes from apoptosis by activating autophagy, and to act as a basal stem cell keratinocyte-protecting drug in irradiated mice.
The effect of sirolimus on mesenchymal cells is unknown, but it is an important issue, since mesenchymal cells such as myofibroblasts and cells promoting vascular calcification play an important role in atherogenesis and vascular restenosis.
Sirolimus seems to block the proliferation and the migration of vascular smooth muscle cells, but we lack information concerning the effects on other cells composing atherosclerotic plaques.
The aim of the present paper is to evaluate the long-term effects of sirolimus, rather than short-term cell survival, on three different cell in vitro models, cultured in Minimum Essential Medium, which simulates physiological conditions (w/o CO2 and glucose, in order to clarify the effectiveness of sirolimus in blocking cell proliferation and survival.
The Pasquinelli Research Team concluded in their Oncotarget Research Paper that the plaque typology and the different cell composition of the plaque, e. g., the presence of inflammatory cells, angiogenesis, prevalence of fibrosis, presence of osteogenic progenitors, may influence the response to sirolimus.
Moreover, it is known that the clonal capacity varies between cells and we should consider this matter when evaluating the effectiveness of eluted stent.
Finally, additional mechanisms can have a role, such as amitotic cell division.
These mechanisms were also observed in human atherogenesis and could be fundamental to evaluate the in vivo effect of sirolimus too.
Full text - https://www.oncotarget.com/article/27554/text/
Correspondence to - Gianandrea Pasquinelli - gianandr.pasquinelli@unibo.it
Keywords - atherosclerosis, cell proliferation, sirolimus, stents
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
The cover for issue 29 of Oncotarget features Figure 5, "In vivo effects of treatment with L-Grb2 in combination with anti-angiogenic therapy in an ovarian tumor model," by Lara, et al. which reported that adaptor proteins such as growth factor receptor-bound protein-2 play important roles in cancer cell signaling. In the present study, the authors examined the biological effects of liposomal antisense oligodeoxynucleotide that blocks Grb2 expression in gynecologic cancer models.
Murine orthotopic models of ovarian and uterine cancer were used to study the biological effects of L-Grb2 on tumor growth.
In vitro experiments were carried out to elucidate the mechanisms and potential predictors of tumor response to L-Grb2. Treatment with L-Grb2 decreased tumor growth and metastasis in orthotopic models of ovarian cancer by reducing angiogenesis and increasing apoptosis at a dose of 15 mg/kg with no effect on mouse body weight.
Reverse-phase protein array analysis identified significant dysregulation of metabolites in ovarian cancer cells after Grb2 downregulation.
L-Grb2 has therapeutic efficacy in preclinical models of ovarian and uterine cancer.
Dr. Anil K. Sood and Dr. Cristian Rodriguez-Aguayo from The University of Texas MD Anderson Cancer Center said, "Adaptor proteins are essential for signal propagation after receptor tyrosine kinase (RTK) activation."
Druggable targets have often been proteins with enzymatically active sites to which small molecules could bind.
However, the ability to target previously undruggable targets is evolving. Small-molecule inhibitors rely on intracellular targets or antibodies to inhibit the activity of growth factors, cell surface receptors, and cytokines.
The development of nucleic acid interference-based therapeutics has allowed for regulation of gene expression to inhibit elusive targets.
Nucleic acid-based therapeutics involves a process in which RNA molecules or antisense oligonucleotides inhibit gene expression or translation by neutralizing targeted mRNA molecules.
After crossing the cell membrane, ASOs target mRNA directly through complementary base pair interactions, in the nucleus or cytosol, thus blocking and neutralizing targeted mRNAs.
The Sood/Rodriguez-Aguayo Research Team concluded in their Oncotarget Research Paper, "we report that L-Grb2 has promising antitumor activity in preclinical models of ovarian and uterine carcinoma.
Whereas the evidence of L-Grb2's activity against hematological malignancies is promising, whether it is active in clinical trials against solid tumors has yet to be tested.
Therapies targeting the ErbB2 receptor have had limited success in ovarian cancer, but L-Grb2 may be a better target given its status as an important converging point for cancer cell signaling pathways."
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27667
Full text - https://www.oncotarget.com/article/27667/text/
Correspondence to - Anil K. Sood - asood@mdanderson.org and Cristian Rodriguez-Aguayo - CRodriguez2@mdanderson.org
Keywords - ovarian cancer, nucleic-acid based therapeutics, therapeutic approaches, uterine cancer
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Oncotarget - Exploring The Role Of Survivin In Neuroendocrine Neoplasms by Oncotarget Podcast
Oncotarget - The Role Of EGFR Mutations In Predicting Recurrence In Lung Adenocarcinoma by Oncotarget Podcast
Oncotarget - Adoptive Cell Therapy In Combination With Checkpoint Inhibitors by Oncotarget Podcast
Oncotarget - Hyperprogression To Immune Blockade Followed By A Response With Cabozantinib by Oncotarget Podcast
Prof. Malka Cohen-Armon and her team at Tel Aviv University's Sackler Faculty of Medicine choose Oncotarget amongst leading medical journals like The New England Journal of Medicine, Nature or The Lancet to publish groundbreaking cancer research.
Here's more: Developing comprehensive granular multi-modal aging clocks will help get a better understanding of the aging processes, establish causal relationships, and identify preventative and recent reports demonstrate an exclusive eradication of a variety of human cancer cells by the modified phenanthridine PJ34.
The efficient eradication of malignant cells in human pancreas cancer xenografts presents a new model of pancreas cancer treatment.
One of the many promising applications of the deep aging clocks built into the generative adversarial networks is generation of synthetic biological data with age as a generation condition.
Dr. Malka Cohen-Armon from the Sackler Faculty of Medicine & the Sagol School of Neuroscience at Tel-Aviv University in Tel-Aviv, Israel said, "Despite a substantial advance in cancer treatment, pancreatic ductal adenocarcinoma (PDAC) have a limited response to current treatments, and a low 5-years survival rate of about 6%."
Furthermore, the authors identified phenanthrenes acting as PARP1 inhibitors that efficiently eradicate a variety of human cancer cells without impairing benign cells.
However, their PARP1 inhibition per-se does not impair nor eradicate human malignant cells, including pancreas cancer cells, PANC1.
In contrast, at higher concentrations than those causing PARP1 inhibition, PJ34, Tiq-A and Phen eradicate a variety of human cancer cells by mitotic catastrophe cell death.
Here, the efficacy of PJ34 to eradicate human pancreas cancer cells is tested in cell cultures and in xenografts.
In xenografts, eradication of human PANC1 cells deduced from a massive reduction of human proteins in the tumors, was measured 30 days after the treatment with PJ34 has been terminated.
The Cohen-Armon Research Team concluded that PJ34, which is permeable in the cell membrane, accessed and eradicated human PDAC cells in xenografts without impairing normal proliferating cells infiltrated into the tumors.
Full text - https://doi.org/10.18632/oncotarget.27268
Correspondence to - Malka Cohen-Armon - marmon@tauex.tau.ac.il
Keywords - PJ34, pancreas cancer, stroma, PANC1 cancer xenografts
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit http://www.oncotarget.com or connect with @Oncotarget
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM
The cover for issue 58 of Oncotarget features Figure 5, "Representative images of KLK6 and HMGA2 IHC staining in the surgical material of a colon cancer patient," by Chen, et al.
In the CRC patients, KLK6 protein levels were elevated in the non-cancerous distant and adjacent tissues, compared to their paired tumor tissues.
Patients with mutant K-RAS tumors had significantly higher level of KLK6 protein in the luminal surface of non-cancerous distant tissue, compared to the corresponding tissues of the patients with K-RAS wild type tumors.
Dr. Natalia A. Ignatenko from the University of Arizona Cancer Center, Tucson, AZ, USA and the Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA said, "Human KLK6, is a member of the kallikrein-related peptidase family of proteins, originally identified and cloned based on its aberrant expression in human breast and ovarian cancer"
As a proteolytic enzyme, KLK6 can contribute to the invasive phenotype of cancer cells via degradation of extracellular matrix proteins, such as collagen, fibronectin, laminin, fibrinogen and activation of matrix metalloproteinases.
The researchers previously reported that introduction of the mutated K-RAS oncogenic driver gene into Caco-2 colon cell line, which express wild type K-RAS, induced KLK6 expression.
Knocking down endogenously overexpressed KLK6 in highly invasive HCT116 cells, which carries K-RAS mutation, was sufficient to decrease the invasive and metastatic properties of this cell line.
In the present study, the authors investigated the consequences of KLK6 overexpression and its enzymatic activity in colon cancer cells.
They found that KLK6 overexpression in colon cancer cells, regardless of its enzymatic activity, induces the expression of transcription associated protein HMGA2, which has been identified as a driver of the CRC progression and metastasis.
The Ignatenko Research Team concluded, "Moreover, disease recurrence was noted in patients with high KLK6 scores and positive HMGA2 staining. Although more robust analysis of the clinical cases is required, our current observations suggest that KLK6 may contribute to the LIN28B-let7-HMGA2 axis and may serve as an early marker of disease recurrence."
Press Release - http://www.oncotarget.com/news/pr/kallikrein-6-protease-advances-colon-tumorigenesis-via-induction-of-the-high-mobility-group-a2-protein
Keywords - colorectal cancer, kallikrein-related peptidase 6 or KLK6, SMAD2/3, epithelial-mesenchymal transition, HMGA2
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit www.oncotarget.com or connect with @OncotargetJrnl
Oncotarget is published by Impact Journals, LLC, please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact media@impactjournals.com 18009220957x105
http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=19269&path[]=61662
The cover for issue 28 of Oncotarget features Figure 5, "TMEM165 expression levels alters N-linked glycosylation," by Murali, et al.
Volume 11, Issue 28 of Oncotarget features "Lipid and protein tumor markers for head and neck squamous cell carcinoma identified by imaging mass spectrometry" by Schmidt et, al. which reported that the authors used MALDI imaging mass spectrometry and immunohistochemistry to seek tumor-specific expression of proteins and lipids in HNSCC samples.
DOI - https://doi.org/10.18632/oncotarget.27649
Full text - https://www.oncotarget.com/article/27649/text/
Correspondence to - Zsolt Balogi - zsolt.balogi@aok.pte.hu and László Márk - laszlo.mark@aok.pte.hu
Keywords - Imaging mass spectrometry, tumor marker, lipid tumor marker, S100A8, S100A9
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Volume 11, Issue 26 of Oncotarget reported that Lung cancer is of particular importance, as it is the deadliest cancer worldwide.
In this study, the authors show that high mi R-708 expression is associated with survival rates in lung squamous cell carcinoma patients. mi R-708 also represses PGE2 production by suppressing both COX-2 and mPGES-1 expression in lung cancer cells.
Moreover, mi R-708 decreases proliferation, survival, and migration of lung cancer cells, which can be partially attributed to mi R-708's inhibition of PGE2 signaling.
Lastly, they identify novel mi R-708 predicted targets and possible regulators of mi R-708 expression in lung cancer.
Collectively, these data demonstrate that dysregulated mi R-708 expression contributes to exacerbated PGE2 production, leading to an enhanced pro-tumorigenic phenotype in lung cancer cells.
Dr. Carol S. Lutz from The Department of Microbiology, Biochemistry, and Molecular Genetics at Rutgers Biomedical & Health Sciences, New Jersey Medical School, School of Graduate Studies in Newark New Jersey USA said, "Lung cancer is the most common cancer, with more than 2.09 million lung cancer cases worldwide in 2018."
More importantly, lung cancer is the deadliest cancer in the world, with more than 1.79 million lung cancer-related deaths in 2018.
Lung cancer is a collection of several distinct subtypes, with non-small cell lung cancer accounting for 85% of all lung tumors. mi R-708 also indirectly regulates the expression of genes involved in PI3K signaling, cell cycle progression, epithelial-mesenchymal transition, and cancer cell stemness.
In this study, the authors aim to decipher novel mi R-708 targets and suggest a solution to the controversy on whether mi R-708 is an oncogenic or tumor-suppressive mi RNA in lung cancer.
The Lutz Research Team concluded in their Oncotarget Research Paper that collectively, their findings suggest further study of mi R-708 in lung cancer.
The data paired with previous studies highlight a potential value for mi R-708 as a diagnostic in differentiating lung tumors, as well as a potential therapeutic intervention, particularly in lung squamous cell carcinomas.
Their work has identified novel tumor-suppressive mi R-708 functions by suppressing oncogenic PGE2 production through targeting of COX-2 and mPGES-1.
These findings could be the foundation for identifying novel mi R-708 targets, as well as regulators of mi R-708 expression in cancer.
Moreover, the study highlights the need to better understand lung cancer biology to improve the diagnosis and treatment of lung cancer, ultimately aiming to increase positive patient outcomes.
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27614
Full text - https://www.oncotarget.com/article/27614/text/
Correspondence to - Carol S. Lutz - lutzcs@njms.rutgers.edu
Keywords - miR-708-5p, miR-708, lung cancer, COX-2, mPGES-1
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Oncotarget Volume 11, Issue 27 reported that Epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition are central to metastatic aggressiveness and therapy resistance in solid tumors.
While molecular determinants of both processes have been extensively characterized, the heterogeneity in the response of tumor cells to EMT and MET inducers has come into focus recently and has been implicated in the failure of anti-cancer therapies.
Recent experimental studies have shown that some cells can undergo an irreversible EMT depending on the duration of exposure to EMT-inducing signals.
While the irreversibility of MET, or equivalently, resistance to EMT, has not been studied in as much detail, evidence supporting such behavior is slowly emerging.
Here, the authors identify two possible mechanisms that can underlie resistance of cells to undergo EMT: epigenetic feedback in ZEB1/GRHL2 feedback loop and stochastic partitioning of biomolecules during cell division.
Identifying the ZEB1/GRHL2 axis as a key determinant of epithelial-mesenchymal plasticity across many cancer types, the authors use mechanistic mathematical models to show how GRHL2 can be involved in both the above-mentioned processes, thus driving an irreversible MET. This study highlights how an isogenic population may contain subpopulation with varying degrees of susceptibility or resistance to EMT, and proposes a next set of questions for detailed experimental studies characterizing the irreversibility of MET/resistance to EMT.
Dr. Herbert Levine from The Center for Theoretical Biological Physics at Rice University as well as The Department of Physics at Northeastern University and Dr. Mohit Kumar Jolly from The Centre for BioSystems Science and Engineering at The Indian Institute of Science said: "Epithelial-Mesenchymal Transition (EMT) is a cell biological process involved in driving cancer metastasis and therapy resistance the two grand clinically unsolved challenges."
These hybrid E/M phenotypes may drive collective cell migration as clusters of tumor cells and can be more aggressive than cells in pure epithelial or mesenchymal phenotypes.
Recent experiments decoding the dynamics of EMT/MET using live-cell imaging and/or induction and withdrawal of various EMT-inducing external signals such as TGF? or tuning the levels of EMT-specific transcription factors have provided important insights into the reversibility of EMT and MET. Cells induced to undergo EMT for shorter durations may revert to an epithelial state after withdrawal of the signal/stimulus.
However, similar investigations about the irreversibility of MET, or in other words, the resistance of epithelial cells to undergo EMT in response to EMT-inducing signals, remain to be done.
Here, the authors' propose two independent mechanism that may explain the resistance of epithelial tumor cells to undergo EMT:
1) epigenetic feedback mediated via GRHL2?an MET-inducing transcription factor ; and 2) stochastic partitioning of parent cell biomolecules among the daughter cells at the time of cell division. Conversely, here, the authors' show that incorporating this epigenetic feedback loop acting on the inhibition of ZEB1 by GRHL2 can cause an irreversible MET. Cells undergoing irreversible MET may exhibit resistance in undergoing EMT when exposed to EMT-inducing signals.
The Levine/Jolly Research Team concluded in their Oncotarget Research Paper that their results offer mechanistic insights into two possible mechanisms that may drive varying degrees of susceptibility and resistance to undergoing EMT in response to an EMT-inducing signal in a given isogenic population. Full text - https://www.oncotarget.com/article/27651/text/
The cover for issue 27 of Oncotarget features Figure 4, "(A) Bimodal imaging examples of control and treated tumors (red) before and after the treatment period," by Browning, et al. and reported that the authors developed a 3-dimensional bioprinted skin model of cutaneous squamous cell carcinoma (cSCC) tumors together with a microscopy assay to test chemotherapeutic effects in tissue.
Fluorescence-derived imaging biomarkers indicated that 50% of cancer cells were killed in the tissue after 1μM 5-Fluorouracil 48-hour treatment, compared to a baseline of 12% for untreated controls.
The imaging biomarkers also showed that normal keratinocytes were less affected by treatment than the untreated tissue, which had no significant killing effect.
Data showed that 5-Fluorouracil selectively killed cSCC cells more than keratinocytes.
The authors' 3DBPS assay platform provides the cellular-level measurement of cell viability and can be adapted to achieve non-destructive high-throughput screening in bio-fabricated tissues.
Dr. Daniel S. Gareau from The Laboratory for Investigative Dermatology at The Rockefeller University, New York said, "Global incidence of cSCC is 2.2 million people and accounts for most of the ~10,000 annual non-melanoma skin cancer deaths in the United States."
Drug discovery for small molecule therapies to treat locally advanced/inoperable or metastatic cSCC and other cancers can be accelerated using patient-specific, physiologically relevant models amenable to high-throughput screening.
Models should mimic the tumor microenvironment, given its influence on tumor progression and metastasis, and should reproduce in vivo tumor cell physiochemical signaling and mechanical cues from the surrounding tissue extracellular matrix.
Animal models may not be readily translatable to human cancer treatment, and three-dimensional tissue culture models offer a viable alternative for pre-clinical screening of small molecule therapeutics.
3D models using human-derived cell lines offer increased complexity and physiological fidelity compared with two-dimensional monocultures and have been developed for several cancer models, including melanoma, pancreatic cancer, and cervical cancer.
In the disease model presented here, A431 cSCC spheroids were introduced into the tissue, and histopathology and cDNA microarray analysis was used to confirm the biological fidelity of the cancer model.
The authors' objective was to quantify the therapeutic efficacy of a standard of care treatment for a cSCC skin tissue model that recapitulates the microenvironment in which this cancer grows.
The Gareau Research Team concluded in their Oncotarget Research Paper that the model described provides a higher degree of clinical relevance because it enables the testing of chemotherapeutics against tumor cell growth in a tissue-specific context, thus capturing any potential interactions between the tumor and its microenvironment.
They envision that this model could be adopted in a “bedside” manner and applied to cells from cSCC patient tumor biopsies.
DOI - https://doi.org/10.18632/oncotarget.27570
Full text - https://www.oncotarget.com/article/27570/text/
Correspondence to - Daniel S. Gareau - dgareau@rockefeller.edu.
Keywords - squamous cell carcinoma, screening, 3D printing, in vitro model, confocal microscopy
About Oncotarget To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Oncotarget Volume 11, Issue 27 published "Clonality and antigen-specific responses shape the prognostic effects of tumor-infiltrating T cells in ovarian cancer" by Tsuji et al. which reported that to delineate the complexity of anti-tumor T-cell responses, the author's utilized a computational method for de novo assembly of sequences from CDR3 regions of 369 high-grade serous ovarian cancers from TCGA, and then applied deep TCR-sequencing for analyses of paired tumor and peripheral blood specimens from an independent cohort of 99 ovarian cancer patients.
In the validation cohort, the authors' discovered that patients with low T-cell infiltration but low diversity or focused repertoires had clinical outcomes almost indistinguishable from highly-infiltrated tumors.
They also found that the degree of divergence of the peripheral repertoire from the TIL repertoire, and the presence of detectable spontaneous anti-tumor immune responses are important determinants of clinical outcome.
Also that the prognostic significance of TILs in ovarian cancer is dictated by T-cell clonality, degree of overlap with peripheral repertoire, and the presence of detectable spontaneous anti-tumor immune response in the patients.
These immunological phenotypes defined by the TCR repertoire may provide useful insights for identifying “TIL-low” ovarian cancer patients that may respond to immunotherapy.
Dr. Kunle Odunsi from The Center for Immunotherapy as well as The Department of Gynecologic Oncology at Roswell Park Comprehensive Cancer Center said, "The presence of tumor-infiltrating lymphocytes (TILs) is a key determinant of clinical outcome in a wide range of solid tumors including ovarian cancer."
High-throughput next-generation sequencing has made it possible to read the entire CDR3 to uniquely identify specific T cell clones and to estimate the absolute frequency of T cell clones in tumor tissue from the copy number of TCR sequences.
The importance of TCR repertoire in shaping anti-tumor immunity in ovarian cancer was recently demonstrated using unbiased functional analysis of TCR repertoires from TILs derived from two patients.
Tumor reactivity was revealed in 0–5% of tested TCRs indicating that the vast majority of T cells infiltrating ovarian tumors were irrelevant for tumor recognition.
To determine how the TCR repertoire of TILs shapes the prognosis of ovarian cancer patients, the authors' utilized a new computational method for de novo assembly of sequences from CDR3 regions using paired-end RNA-seq data from the Cancer Genome Atlas study of high-grade serous ovarian cancers.
The author's examined TCR repertoire in the context of the degree of tumor infiltration by T cells, spontaneous immune responses against bona fide TAAs, and clinical outcome.
The Odunsi Research Team concluded in their Oncotarget Research Paper that despite these limitations, this study highlights the extraordinary diversity of the T-cell repertoire in ovarian cancer patients, and demonstrates that pre-existing immunity against cancer antigen is a critical prerequisite to correctly understand the prognostic significance of the T-cell repertoire in the tumor and peripheral blood of patients with ovarian cancer.
They have distilled TCR repertoire information into candidate biomarkers that may critically influence the prognosis of ovarian cancer patients.
Conceptually, ovarian cancers may not fit into the classic paradigm of ?cold' and ?hot' based on the number of T cells they contain, but also by the TCR repertoire information, which serves as a surrogate for tumor recognition.
The latest technologies put these prognostic features in clinical reach not only for predicting prognosis but potentially for determining the best immunotherapeutic strategy for each patient. Full text - https://www.oncotarget.com/article/27666/text/
Correspondence to - Kunle Odunsi - kunle.odunsi@roswellpark.org.
Keywords - T-cell repertoire, ovarian cancer, tumor immunity
Oncotarget Volume 11, Issue 27 published "Correction of the NSE concentration in hemolyzed serum samples improves its diagnostic accuracy in small-cell lung cancer" by Genet et al. which reported that this study aimed to develop a hemolysis correction equation and evaluate its role in small-cell lung cancer (SCLC) diagnostics.
A hemolysis correction equation was obtained by analyzing the relationship between the measured Neuron-specific enolase (NSE) concentration and the degree of hemolysis.
Correction of the measured NSE concentration in patients suspected of lung cancer caused an increase in AUC and a significantly lower cut-off value for SCLC detection when compared to uncorrected results.
Therefore, a hemolysis correction equation should be used to correct falsely elevated NSE concentrations.
Application of the equation illustrates the importance of hemolysis correction in SCLC diagnostics and questions the correctness of the currently used diagnostic cut-off value.
Dr. Daan van de Kerkhof from The Catharina Hospital Eindhoven as well as The Máxima Medical Center said, "Neuron-specific enolase (NSE) is a dimeric metalloenzyme which functions as a cell specific isoenzyme of the glycolytic enzyme enolase."
Furthermore, improved discrimination of the two main lung cancer subtypes, SCLC and non-small cell lung cancer was achieved when applying a diagnostic cut-off value of 25 ng/mL NSE or analyzing multiple protein tumor markers such as NSE and progastrin-releasing peptide at the same time.
Considering the use of NSE in lung cancer diagnostics and the medical actions that may follow, accurate and reliable quantification of NSE is of main importance.
However, previous studies evaluating the prognostic value of NSE in lung cancer diagnostics did not apply exclusion criteria or did not include the effect of hemolysis on the measured NSE concentration as such, while other factors that could influence serum tumor marker concentrations were addressed.
Therefore, this study aimed to develop, validate and apply a hemolysis correction equation that nullifies the effect of hemolysis on NSE quantification in samples of adult patients.
Using this equation, the effect of hemolysis correction on the NSE cut-off value in SCLC diagnostics was evaluated and the maximum acceptable degree of hemolysis for reliable correction was established.
The Kerkhof Research Team concluded in their Oncotarget Research Paper, "this study demonstrates that a hemolysis correction equation improves diagnostic accuracy of serum NSE concentrations in patients suspected of lung cancer. A hemolysis correction equation is therefore suggested to be incorporated in NSE-based clinical decision making, bearing in mind that results of samples with an H-index above 30 μmol/L should not be reported to clinicians."
DOI - https://doi.org/10.18632/oncotarget.27664
Full text - https://www.oncotarget.com/article/27664/text/
Correspondence to - Daan van de Kerkhof - daan.vd.kerkhof@catharinaziekenhuis.nl.
Keywords - small-cell lung cancer, protein tumor markers, neuron-specific enolase, hemolysis correction equation
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Oncotarget Volume 11, Issue 27 published "Australian experience of peptide receptor radionuclide therapy in lung neuroendocrine tumours" by Lim et al. which reported peptide receptor radionuclide therapy (PRRT) is an approved treatment modality for gastroenteropancreatic neuroendocrine tumours, although Phase III randomised clinical trial data is not available for NETs of other site of origin, in practice, PRRT is used more widely in clinical practice, based on its mechanism of targeting the somatostatin receptor.
A retrospective chart review of patients with TC and AC who received 177Lu-dotatate PRRT between January 2002 and June 2019 in six hospitals across Australia was undertaken.
Forty-eight patients received a median of four 177Lu-dotatate treatments. The response rate to 177Lu-dotatate was 33%, with a median overall survival of 49 months, at a median follow up of 33 months. 177Lu-dotatate PRRT in patients with lung NETs is used in real world practice, where it appears well-tolerated with some efficacy. Dr. Lisi Elizabeth Lim from The Department of Medical Oncology at Monash Health said "Neuroendocrine tumours (NETs) are uncommon malignancies, comprising 0.5% of all cancers."
Lung is the primary site for approximately 20?25% of NETs; conversely NETs comprises about 2% of all lung malignancies.
New trials have demonstrated that adequate numbers of patients can be recruited through global collaborations, both for protocols specific to lung NETs and those recruiting patients with NETs from a variety of sites.
PRRT is a firmly established treatment modality for advanced GEP NETs following the publication of the landmark NETTER-1 trial, where patients with progressive midgut NET were randomised to receive 177Lu-dotatate with ongoing octreotide long-acting repeatable therapy, or high dose octreotide LAR alone.
The significant benefit for PRRT in midgut NETs has provoked debate about whether randomised trials are required to prove its efficacy in NETs of other site of origin.
NET consensus guidelines either omit specific comment on the use of PRRT in lung NETs, or state that imaging with SSTR-PET can assist in identifying patients who may benefit from PRRT. The Lim Research Team concluded in their Oncotarget Research Paper that further data will be forthcoming also from studies of PRRT in patients with SSTR-expressing tumours of histologies other than NET. The randomised phase II LUTHREE trial is inclusive of all SSTR positive tumour types, and is not restricted to NETs. The POLNETS trial is also extending the use of PRRT to paraganglioma and pheochromocytoma, in addition to advanced NETs of any site of origin.
DOI - https://doi.org/10.18632/oncotarget.27659
Full text - https://www.oncotarget.com/article/27659/text/
Correspondence to - Lisi Elizabeth Lim - elizabeth.lisi.lim@gmail.com.
Keywords - lung, carcinoid, atypical, neuroendocrine, peptide receptor radionuclide therapy
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Volume 11, Issue 26 of Oncotarget reported that in this study the authors studied the differences in mi RNA expression between sporadic and FAP-associated Desmoid tumors using microarray confirmed by quantitative PCR.
Among them, mi R-133b levels were significantly lower in FAP-associated Desmoid tumors than in sporadic Desmoid tumors. The qPCR analysis showed that SIRT1 mRNA levels were significantly up-regulated in FAP-associated Desmoid tumor than in sporadic Desmoid tumor, whereas no differences in ELAVL1 expression was observed between these two Desmoid tumor types.
In addition, a negative correlation was observed between mi R-133b and SIRT1 in FAP-associated Desmoid tumors, but not in sporadic Desmoid tumors The mi R-133b-SIRT1-β-catenin axis may represent a novel mechanism underlying progression of FAP-associated Desmoid tumor.
Dr. Maria Teresa Rotelli from The Department of Emergency and Organ Transplantation at The University of Bari “Aldo Moro” in Bari Italy said, "Desmoid tumor (DT) is a rare, mesenchymal benign tumor, characterized by monoclonal, fibroblastic proliferation with local invasiveness, high risk of recurrence and even mortality, despite metastatization never occurs."
The CNNTB1 mutations have been found in approximately 85% of DTs by routine Sanger sequencing, however, using a highly sensitive technique like next-generation sequencing, they may account for 90–95% of sporadic DT cases.
In these DTs, the germline mutations in the APC gene are responsible for the nuclear accumulation of β-catenin.
While the risk of death in sporadic DT is low, FAP-associated DTs are the most frequent cause of death in patients with FAP after the colon has prophylactically been removed.
It must be emphasized that the disruption of the Wnt signaling represents a common pathway in both DT forms, but sporadic and FAP-associated DTs are associated with mutually exclusive molecular alterations.
In a previous study, the authors have investigated a possible correlation between mi RNA expression and CTNNB1 mutations in sporadic DTs.
The Rotelli Research Team concluded in their Oncotarget Research Paper that the dialog between MSCs and tumor cells in FAP-associated DT tissue microenvironment could lead to β-catenin deacetylation driven by SIRT1, promoting Wnt/β-catenin signaling cascade in this tumor.
Although the number of specimens of FAP-associated DTs used in the present study was limited, it could be speculated that the β-catenin deacetylation process in FAP-associated DTs mimics the stabilization of that protein induced by CTNNB1 gene mutations occurring in sporadic DTs.
Therefore, in addition to APC gene mutations, the mi R-133b-SIRT1-β-catenin axis may represent a novel mechanism underlying the progression of FAP-associated DT. However, further studies are needed to fully understand the influence of mi R-133b-SIRT1 in the genesis or progression of FAP-associated DT.
DOI - https://doi.org/10.18632/oncotarget.27622
Full text - https://www.oncotarget.com/article/27622/text/
Correspondence to - Maria Teresa Rotelli - mariateresa.rotelli@uniba.it
Keywords - desmoid tumor, miRNA, familial adenomatous polyposis, B-catenin, Wnt pathway
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Oncotarget: IQGAP1 control of centrosome function defines variants of breast cancer
The cover for issue 26 of Oncotarget features Figure 6, "Mislocalization of IQGAP1-BRCA1 in human TNBC tumors phenocopies the dominant mutants and the TNBC cells," by Osman, et al. and reported that IQGAP1 is a signaling scaffold implicated in TNBC, but its mechanism is unknown.
Genetic mutant analyses suggest that phosphorylation cycling of IQGAP1 is important to its subcellular localization and centrosome-nuclear shuttling of BRCA1; dysfunction of this process defines two alternate mechanisms associated with cell proliferation.
TNBC cell lines and patient tumor tissues differentially phenocopy these mechanisms supporting the clinical existence of molecularly distinct variants of TNBC defined by IQGAP1 pathways.
The authors discuss a model in which IQGAP1 modulates centrosome-nuclear crosstalk to regulate cell division and imparts on cancer.
These findings have implications on cancer racial disparities and can provide molecular tools for classification of TNBC, presenting IQGAP1 as a common target amenable to personalized medicine
Dr. Mahasin A. Osman from The Department of Medicine, Division of Oncology, Health Sciences Campus at The University of Toledo as well as The Department of Molecular Pharmacology, Physiology and Biotechnology, Division of Biology and Medicine at Warren Alpert Medical School of Brown University said, “The triple-negative breast cancer (TNBC) is a highly heterogeneous group of diseases defined by absence of expression of growth factor and hormonal receptors, and thus it is highly lethal due to lack of diagnostic markers and therapeutic targets.”
In vitro depletion of BRCA1 results in amplified centrosomes, a phenotype observed in early-stage tumors, including breast cancer, but how might wild type BRCA1 protein control centrosome amplification is unclear.
While increased centrosome size resulting from PCM expansion has been reported as abnormality in human tumors, increased centrosome number is observed in 20–30% of tumors that overexpress oncogenes or lack tumor suppressors like BRCA1.
Centrosome amplification has been associated with high-grade tumors and poor prognosis and was suggested as a biomarker for advanced cancer.
Expression of dominant active mutants of IQGAP1 associates with amplified centrosomes while the expression of dominant-negative mutants associates with increased centrosome size.
The authors discuss a model whereby IQGAP1 acts as a signaling scaffold in the centrosome and influences centrosome protein transport, dysfunction of which underlie centrosome aberrations in cancer thereby presenting IQGAP1 as a common target in variants of TNBC, amenable to personalized medicine.
The Rotelli Research Team concluded in their Oncotarget Research Paper that taken together, the findings of this study underscore the importance of the delicate balance of expression, localization and/or modification of IQGAP1-BRCA1 and centrosome proteins in cell homeostasis and support that IQGAP1 influences BRCA1 transport or anchorage.
IQGAP1 may serve as a regulatory scaffold for BRCA1 and other centrosomal proteins to regulate their stability or transport between the nucleus and the centrosome, a mechanism by which it modulates nuclear-centrosome crosstalk during the cell cycle and thus regulates cell proliferation.
Furthermore, as IQGAP1 has been implicated in various carcinomas, the mechanisms discussed here likely apply to a wide range of carcinoma, thus presenting IQGAP1 as a non-organ-specific clinical target amenable to precision medicine
DOI - https://doi.org/10.18632/oncotarget.27623
Full text - https://www.oncotarget.com/article/27623/text/
Correspondence to - Mahasin A. Osman - Mahasin.Osman@UToledo.Edu, Mahasin_Osman@brown.edu.
Keywords - IQGAP1, BRCA1, β-catenin, MNK1, triple negative breast cancer
Volume 11, Issue 25 of @Oncotarget reported that Administration of landiolol hydrochloride was found to be associated with reduced incidence of atrial fibrillation after esophagectomy for esophageal cancer in our previous randomized controlled trial.
Between March 2014 and January 2016, 100 patients with esophageal cancer were registered in an RCT trial and randomly allocated to receive either administration of landiolol or a placebo.
The authors analyzed data from this RCT to better understand the effect of postoperative AF and severe associated complications on overall survival after esophagectomy for cancer.
In multivariate analysis, high stage alone was an independent prognostic factor for esophageal cancer patients the following esophagectomy.
Dr. Toshiyasu Ojima from The Wakayama Medical University said, "Esophagectomy is considered the optimum treatment against esophageal cancers."
The incidence of major postoperative complications in our previous study increased in patients that developed new-onset AF following subtotal esophagectomy.
The effect of postoperative AF on long-term survival following esophagectomy is therefore controversial.
Severe postoperative complications may make patients with esophageal cancer less likely to survive over the long term.
Patients with esophageal cancer but without severe postoperative complications have been shown to have better long-term survival than patients with complications.
The authors also evaluate the influence of severe postoperative complications on overall survival and whether prophylactic administration of landiolol hydrochloride directly influences prolonged survival in patients with esophageal cancer.
The Ojima Research Team concluded in their Oncotarget Research Paper, "new-onset AF and other severe complications were not associated with poorer long-term survival after esophagectomy. In addition, administration of landiolol hydrochloride after esophagectomy did not contribute to the prolonged OS of patients with esophageal cancer."
DOI - https://doi.org/10.18632/oncotarget.27643
Full text - https://www.oncotarget.com/article/27643/text/
Correspondence to - Toshiyasu Ojima - tojima@wakayama-med.ac.jp
Keywords - esophageal cancer, atrial fibrillation, landiolol, randomized controlled trial, complication
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Volume 11, Issue 25 of @Oncotarget reported that the present study was aimed at evaluating the hypothesis that p53 governs the expression and activation of the INSR gene in breast cancer cells.
The availability of MCF7 breast cancer-derived cell lines with specific disruption of either the insulin-like growth factor-1 receptor or INSR allowed us to address the impact of the IGF1R and INSR pathways on p53 expression.
Wild-type p53 stimulated INSR promoter activity in control cells while disruption of endogenous IGF1R or INSR led to inhibition of promoter activity by p53.
Mutant p53 strongly stimulated INSR promoter.
Furthermore, p53 directly binds to the INSR promoter in cells with a disrupted IGF1R.
Dr. Haim Werner from Tel Aviv University said, "The insulin/insulin-like growth factors (IGFs) create a hormonal network responsible for the regulation of important physiological events throughout life."
The classical view that emerged following the cloning and characterization of the INSR and IGF1R genes in the mid-1980s postulated that activation of INSR by insulin leads, predominantly, to metabolic activities.
One of the cardinal questions still in need of a biologically plausible rationalization is why the INSR and IGF1R, even though they share the majority of their downstream cytoplasmic targets and signaling pathways, are yet responsible for mediating distinct physiological and pathological activities.
Given the emerging evidence of proliferative and potentially anti-apoptotic actions of INSR, the authors investigated in the present paper the regulation of the INSR gene promoter by wild-type and mutant p53 in breast cancer cells.
Using cells with specific disruption of the INSR or IGF1R, the authors also assessed the effect of each one of these signaling pathways on p53 expression and activity.
The data indicate that: activation of p53 is negatively regulated by IGF1R, as indicated by the augmented phosphorylation of p53 in IGF1R-KD cells; p53 directly binds to the INSR promoter region in cells with a disrupted IGF1R; wild-type p53 represses INSR promoter activity in IGF1R-KD and INSR-KD cells while enhancing promoter activity in control cells; mutant p53 stimulates INSR promoter activity in breast cancer cells.
The Werner Research Team concluded in their Oncotarget Research Paper, "we have presented evidence that the INSR gene constitutes a downstream target for p53 action. Whereas wild-type p53 stimulated INSR promoter activity in control MCF7 cells, disruption of endogenous IGF1R or INSR led to inhibition of promoter activity by wild-type p53. Mutant, oncogenic versions of p53, for the most part, strongly stimulated INSR promoter. In addition, p53 exhibits direct binding to the INSR promoter region in cells with a disrupted IGF1R. Taken together, data presented here identifies complex functional and physical interactions between p53 and the INSR pathway. The clinical implications of this interplay in breast cancer needs to be critically assessed."
DOI - https://doi.org/10.18632/oncotarget.27645
Full text - https://www.oncotarget.com/article/27645/text/
Correspondence to - Haim Werner - hwerner@post.tau.ac.il
Keywords - insulin, insulin-like growth factor-1 (IGF1), insulin receptor, IGF1 receptor, p53
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Volume 11 Issue 25 of @Oncotarget reported that the authors aimed to characterize the bacteriome, mycobiome, and mycobiome-bacteriome interactions of oral wash in Head and neck squamous cell carcinoma, or HNSCC, patients and to determine if they are distinct from those of the oral wash of matched non-Head and neck squamous cell carcinoma patients.
Oral wash samples were collected from 46 individuals with HNSCC and 46 controls for microbiome analyses.
A number of organisms were identified as being differentially abundant between oral wash samples from patients with HNSCC and oral wash samples from those without HNSCC. Of note, strains of Candida albicans and Rothia mucilaginosa were differentially abundant and Schizophyllum commune was depleted in those with HNSCC compared to oral wash from those without HNSCC. Our results suggest that the oral cavity of HNSCC patients harbors unique differences in the mycobiome, bacteriome, and microbiome interactions when compared to those of control patients.
Dr. Charis Eng from The Cleveland Clinic as well as The Case Western Reserve University School of Medicine said, "Head and neck squamous cell carcinoma (HNSCC) refers to cancer arising from the squamous epithelium of the oral cavity, pharynx, nasopharynx, and larynx."
Not all patients with these risk factors develop HNSCC, and some patients with HSNCC lack these risk factors.
There is, therefore, a need to identify additional risk factors to better predict which patients, particularly among those at high risk, will develop HNSCC. The oral microbiome contains not only bacterial communities but also fungal communities comprising the oral mycobiome.
Fungal communities have the potential not only to independently influence the environment of the oral cavity but also to interact with oral bacterial communities.
Therefore, the authors sought to identify and characterize differences in the bacteriome and mycobiome profiles of patients with HNSCC versus healthy cancer-free patients, using oral wash as template biospecimen.
The Eng Research Team concluded in their Oncotarget Research Paper that they found inter and intra-kingdom correlations within the oral wash.
Although the composition of the clusters within networks appeared largely similar between case and control oral wash, there were some interactions that differed.
A positive relationship between two organisms could suggest that they occupy similar niches or even that they share a symbiotic relationship.
A negative relationship, by contrast, could point to two organisms that either compete against each other through varying means.
They went on to note multiple interactions that were opposing when considering case oral wash versus control oral wash suggests not only changes in the composition of the microbiome but also in how members of the microbiome interact with each other in HNSCC patients.
The relationship between Alloscardovia and Candida, for example, was negative, in case oral wash but positive in control oral wash.
Such shifts could signal the presence of HNSCC in an oral wash based screening tool for Head and neck squamous cell carcinoma.
DOI - https://doi.org/10.18632/oncotarget.27629
Full text - https://www.oncotarget.com/article/27629/text/
Correspondence to - Charis Eng - engc@ccf.org
Keywords - microbiome, bacteriome, mycobiome, head and neck squamous cell carcinoma, cancer
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Volume 11 Issue 25 of @Oncotarget reported that Indoximod has shaped the understanding of the biology of IDO1 in the control of immune responses, though its mechanism of action has been poorly understood.
Indoximod can have a direct effect on T cells, increasing their proliferation as a result of mTOR reactivation.
Further, indoximod modulates the differentiation of CD4+ T cells via the aryl hydrocarbon receptor, which controls transcription of several genes in response to different ligands including kynurenine.
Indoximod increases the transcription of RORC while inhibiting transcription of FOXP3, thus favoring differentiation to IL-17-producing helper T cells and inhibiting the differentiation of regulatory T cells.
Indoximod can also downregulate expression of IDO protein in vivo in murine lymph node dendritic cells and in vitro in human monocyte-derived dendritic cells via a mechanism that involves signaling through the Ah R. Together, these data improve the understanding of how indoximod influences the effects of IDO, beyond and distinct from direct enzymatic inhibition of the enzyme.
Dr. Erik L. Brincks from NewLink Genetics Corporation as well as Lumos Pharma, Inc. said "Indoleamine 2,3-dioxygenase (IDO1) plays an important role in the regulation of acquired local and peripheral immune tolerance in normal and pathological scenarios."
In cancer, IDO1 can be expressed either directly by the tumor cells or induced indirectly in host antigen presenting cells by the tumor.
IDO1 expression by tumor cells has been associated with significantly worse clinical prognosis and reduced survival in malignant melanoma, pancreatic cancer, ovarian cancer, both pediatric and adult acute myelogenous leukemia, colorectal cancer, prostate cancer, endometrial cancer, and others.
The cellular pharmacodynamic effects of IDO1 activity include the inhibition of antigen-specific CD8+ T cell proliferation, stimulation of differentiation of na�ve CD4+ T cells to Fox P3+ regulatory T cells, the activation of Tregs, and the recruitment of MDSC to the tumor.
Both isomers are capable of restoring T-cell proliferation in an MLR assay with IDO+ dendritic cells as the stimulator cells, or in syngeneic antigen-dependent T-cell proliferation assays using IDO+ dendritic cells isolated from tumor-draining lymph nodes.
L1m T is a competitive inhibitor and substrate of IDO1 enzymatic activity in cell-free assays using purified recombinant IDO1 enzyme, and in tumor cells treated with INFγ or in tumor cell lines transfected with expression vectors that encode IDO1 under the control of an heterologous promoter.
The Brincks Research Team concluded in their Oncotarget Research Paper that these effects are independent on the Trp metabolizing activity of IDO and/or TDO but happen to oppose the effects of the enzymatic activity of IDO and TDO by multiple mechanisms that act on cell types commonly affected by the IDO and TDO pathways.
Indoximod creates a Trp-sufficiency signal which leads to reactivation of MAP4K3 which leads to activation of mTORC1 activity, thus opposing and bypassing the effects of Trp deprivation that lead to GCN2 activation and MAP4K3 and mTOR inactivation.
This effect requires a relatively high concentration of indoximod, is observed in both CD4+ and CD8+ T cells and leads to an increase in the proliferative capacity of activated effector and helper T cells.
This effect takes place at clinically relevant concentrations of indoximod and is independent of IDO/TDO activity or exogenous Kyn, though it happens to oppose the Kyn/Ah R effects on T cell differentiation.
Full text - https://www.oncotarget.com/article/27646/text/
Volume 11, Issue 25 of @Oncotarget reported that to examine the role of RSK in AML, the authors analyzed apoptosis and the cell cycle profile following treatment with BI-D1870, a potent inhibitor of RSK. BI-D1870 treatment increased the G2/M population and induced apoptosis in Acute Myeloid Leukemia cell lines and patient Acute Myeloid Leukemia cells.
Therefore, the authors investigated whether BI-D1870 potentiates the anti-leukemic activity of vincristine by targeting mitotic exit.
Combination treatment of BI-D1870 and vincristine synergistically increased mitotic arrest and apoptosis in acute leukemia cells.
These data show that BI-D1870 induces apoptosis of AML cells alone and in combination with vincristine through blocking mitotic exit, providing a novel approach to overcoming vincristine resistance in AML cells.
Dr. Kathleen M. Sakamoto from Stanford University School of Medicine said, "Acute myeloid leukemia (AML) is a genetically and phenotypically heterogeneous hematologic malignancy characterized by the accumulation of immature myeloid blasts with resultant peripheral blood cytopenia."
Treatment of cells with microtubule targeting agents, including paclitaxel and the vinca alkaloid vincristine, blocks the proper formation of the mitotic spindle through inhibition of microtubule dynamics, resulting in the prolonged mitotic arrest of cancer cells.
MTAs-treated mitotic arrested cells may undergo apoptosis in mitosis, however, the rapid degradation of Cyclin B due to an insufficient SAC leads to the mitotic slippage into tetraploid G1 stage in resistant cells.
Though vinca alkaloid microtubule-destabilizing compounds have shown clinical efficacy against various hematological malignancies and were included in combination chemotherapy of the VAPA study, they are not currently used in induction chemotherapy for AML due to their high toxicity against lymphoid cells and rapid degradation by myeloperoxidase in AML cells.
In this study, they demonstrate that BI-D1870, a potent inhibitor of RSK, induces mitotic arrest, and apoptosis in AML cells without inhibiting CDC2 and CDC25C. Furthermore, BI-D1870 synergizes with vinca alkaloid vincristine in AML cells, suggesting that inhibition of mitotic exit with BI-D1870 could be a promising novel approach for AML therapy in combination with MTAs.
The Sakamoto Research Team concluded in their Oncotarget Research Paper that BI-D1870 is a reversible pan-RSK inhibitor, showing > 500-fold higher activity for RSK than other AGC kinases.
BI-D1870 also inhibits the activity of PLK1, Aurora-B, MELK, PIM3, MST2, and GSK3β at higher concentrations than for RSK. BI-D1870 and BRD7389 have been reported to inhibit proliferation and significantly increase the G2/M population in melanoma cells.
BI-D1870 does not have proper physicochemical properties for clinical application.
Future structure-activity relationships study for BI-D1870 is required to improve solubility and pharmacokinetic profiles for in vivo preclinical and clinical studies.
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27630
Full text - https://www.oncotarget.com/article/27630/text/
Correspondence to - Kathleen M. Sakamoto - kmsakamo@stanford.edu
Keywords - acute myeloid leukemia, BI-D1870, RSK, vincristine, spindle assembly checkpoint
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Volume 11 Issue 25 of @Oncotarget reported that this study aimed to define the mutation profile of SUM in Caucasians.
Next-generation sequencing-based genomic analysis was used to identify frequently mutated loci in 50 cancer-related genes in 31 SUM primary tumors.
The most abundant mutations in SUM were found in KIT – in 13% of cases and NRAS – also in 13%, while BRAF - only in 3% of cases.
The authors' findings confirmed a high frequency of KIT and NRAS mutations in SUM, as well as a low incidence of BRAF mutations.
They reported novel KRAS, CTNNB1, TP53, ERBB2, and SMAD4 mutations in SUM.
Dr. Aneta Borkowska from The Maria Sklodowska-Curie National Research Institute of Oncology said "Across all human cancers, cutaneous malignant melanoma (MM) genome has one of the highest prevalence of somatic mutations."
At the same time, NRAS mutations are detected in approximately 20% of MM and are more commonly reported in melanomas developing in the skin with chronic sun exposure.
WHO Classification of Skin Tumours recognizes the most common acral melanoma histotype is acral lentiginous melanoma, followed by nodular cutaneous melanoma and superficial spreading melanoma.
Cutaneous MM located on the acral part of extremities - hand and foot melanoma - comprises a rare group within all melanomas in Caucasians.
Whole-genome sequencing study shown that structural changes and mutational signature of acral melanomas were dominated by different than other MMs sites.
SUM seems to be not related to sun exposure, however, in Australian Melanoma Genome Project UVR signatures on acral melanomas occurred most frequently in subungual parts.
The Borkowska Research Team concluded in their Oncotarget Research Paper, "Our study offers new insights into the genetics SUM subtype, for understanding pathogenesis and providing potential biomarkers for future studies. Molecular testing is now widely used in patients with advanced melanoma in the process of therapeutic decisions. Mutations reported in melanoma cells provide starting points for the development of the rational design of novel therapies, including immunotherapy agents. They also may provide to find the molecular pathogenesis and natural history of subtypes of this heterogeneous disease. We confirmed that SUM have different than other cutaneous melanomas genetic profile, which due to its rareness and lack of studies should be subjected to further analyzes in multicenter studies."
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27642
Full text - https://www.oncotarget.com/article/27642/text/
Correspondence to - Aneta Borkowska - anetame@gmail.com
Keywords - melanoma, acral melanoma, subungual melanoma, nail apparatus melanoma, SMAD4
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
The cover for issue 24 of Oncotarget features Figure 4, "Cancer-specific survival curves based on GNRI according to pTNM stage," by Hirahara, et al.
Volume 11 Issue 24 of @Oncotarget reported that this study aimed to evaluate the relationship between preoperative Geriatric Nutritional Risk Index and long-term outcomes in elderly gastric cancer patients.
In the univariate analyses, OS was significantly associated with the American Society of Anesthesiologists Physical Status, tumor size, tumor differentiation, pathological stage, carcinoembryonic antigen, C-reactive protein, postoperative complications, and GNRI, whereas in the univariate analyses of CSS, ASA-PS, tumor size, tumor differentiation, pathological stage, CEA, postoperative adjuvant chemotherapy, and Geriatric Nutritional Risk Index were significantly associated with poor prognosis.
In the multivariate analysis, ASA-PS, tumor differentiation, pathological stage, and GNRI were significant independent prognostic factors of OS, whereas ASA-PS, pathological stage, and CEA were significant independent prognostic factors of CSS. Geriatric Nutritional Risk Index is significantly associated with OS and CSS in elderly gastric cancer patients and is an independent predictor of OS. It is a simple, cost-effective, and promising nutritional index for predicting OS in elderly patients.
Dr. Noriyuki Hirahara from The Department of Digestive and General Surgery at Shimane University Faculty of Medicine said "The tumor–node–metastasis (TNM) staging has been the global standard for estimating cancer cell dissemination."
The impact of the nutritional status on the outcome of cancer patients has been intensively studied in recent years, and several assessment tools have been proposed for nutritional screening.
However, the usefulness of these tools has not been fully evaluated in elderly patients.
The geriatric nutritional risk index was developed as a simple and objective nutritional assessment tool for hospitalized elderly patients based on their body weight and serum albumin level.
Therefore, the authors believe that the Geriatric Nutritional Risk Index accurately reflects the nutritional status of elderly cancer patients who are at risk of malnutrition because of their physiological frailty and vulnerability.
The principal aim of this study was to evaluate the prognostic significance of the preoperative Geriatric Nutritional Risk Index for estimating the postoperative outcomes of elderly gastric cancer patients.
The Hirahara Research Team concluded in their Oncotarget Research Paper that in Japan, which has an aging society, an individualized treatment strategy for gastric cancer is indispensable because there are many deaths caused by other diseases.
Recently, sarcopenia has been reported to affect the incidence of adverse events with chemotherapy and the continuation of treatment, leading to a worse prognosis.
Sarcopenia, the age-related loss of skeletal muscle mass and strength, was identified based on cross-sectional computed tomography images at the L3 level.
However, the Geriatric Nutritional Risk Index can be easily calculated from routine laboratory data and physical measurements.
The clinical significance of GNRI, as an indicator of OS, will be increasingly important in the future. DOI - https://doi.org/10.18632/oncotarget.27635
Full text - https://www.oncotarget.com/article/27635/text/
Correspondence to - Noriyuki Hirahara - norinorihirahara@yahoo.co.jp
Keywords - geriatric nutritional risk index, overall survival, cancer-specific survival, gastric cancer, elderly patients
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open-access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or visit www.twitter.com/oncotarget Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Volume 11, Issue 22 of Oncotarget reported that despite relevant medical advancements, metastatic breast cancer remains an incurable disease.
HER2 signaling conditions tumor behavior and treatment strategies of HER2 expressing breast cancer.
Cancer treatment guidelines uniformly identify dual blockade with pertuzumab and trastuzumab plus a taxane as best first line and trastuzumab emtansine as a preferred second-line choice.
However, there is no prospectively designed available study focusing on the sequence and outcomes of patients treated with T-DM1 following the triplet.
In the following report, data concerning a wide series of patients treated in a real-life setting are presented.
Results obtained in terms of response and median progression-free survival suggests a significant role for T-DM1 in disease control of metastatic HER2 expressing breast cancer.
Dr. Salvatore Del Prete from the Medical Oncology Unit “San Giovanni di Dio” Hospital, Frattamaggiore as well as Dr. Liliana Montella from the Medical Oncology Unit “Santa Maria delle Grazie” Hospital said, "From the 80s, Human Epidermal Growth Factor Receptor 2 (HER2) signaling was increasingly recognized as pivotal in tumor growth of HER2 expressing breast cancer. HER2 expression is limited to a proportion (15–20%) of breast cancer; however, HER2 conditions tumor behavior and addresses treatment strategies." Currently available guidelines in metastatic HER2 positive breast cancer design a sequence of treatment with first-line double blockade with trastuzumab plus pertuzumab and a taxane according to Cleopatra trial results and second-line treatment with trastuzumab emtansine enforced by Emilia trial results and, then, lapatinib plus capecitabine.
The reduced toxicity of T-DM1 in the second and later lines of treatment together and the high rates of activity and efficacy are determinant in choosing treatment for a patient candidate to a prolonged time on treatment.
On February 22, 2013, the Food and Drug Administration approved T-DM1 for use as a single agent in the treatment of patients with HER2-positive metastatic breast cancer who previously received trastuzumab and a taxane.
Such results induced FDA on May 3, 2019, to approve T-DM1 for the adjuvant treatment of patients with HER2-positive early breast cancer treated with neoadjuvant taxane and trastuzumab-based treatment and having a residual invasive disease in the breast or axilla at the surgery.
In the present study, data coming from different centers concerning patients with HER2 positive metastatic breast cancer treated with second-line T-DM1 following trastuzumab and pertuzumab were collected and evaluated.
The Del Prete/Montella Research Team concluded in their Oncotarget Research Article that despite the increased rate of survival of metastatic breast cancer patients overall, a rate of patients is lost at any line of therapy.
In two different studies concerning patients series treated predominantly before 2010, 3% and 26% of patients reached the goal of third-line treatment.
This evidence underscores the need to give our patients the best treatment as early as possible.
Summarizing, the available evidence is substantially in favor of the choice of T-DM1 in the treatment of HER2 breast cancer at second and later lines.
DOI - https://doi.org/10.18632/oncotarget.27603
Full text - https://www.oncotarget.com/article/27603/text/
Correspondence to - Salvatore Del Prete - salvatore.delprete@aslnapoli2nord.it and Liliana Montella - liliana.montella@aslnapoli2nord.it
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget
Volume 11, Issue 22 of Oncotarget reported that the goal of this study was to explore the involvement of mi RNAs in beneficial effects exerted by physical activity in breast cancer prevention.
The levels of extracellular mi RNAs were evaluated in blood plasma before and after structured exercise by means of microarray analysis of 1,900 mi RNAs identifying mostly modulated mi RNAs. The different expressions of two mi RNAs involved in breast cancer progression, i. e. up-regulation of mi R-206 and down-regulation of anti-miR-30c, were the most striking effects induced by exercise.
The biological effects of these mi RNAs were investigated in MCF-7 human breast cancer cells.
The evaluation of these mi RNAs in the blood can be used as non-invasive biomarkers for breast cancer prevention.
Dr. Alessandra Pulliero from the Department of Health Sciences at The University of Genoa said, "The relevance of structured exercise for public health has been addressed by the World Health Organization, and its lack is estimated to be the main risk factor for 21–25% of breast and colon cancer cases, 27% of diabetes cases, and 30% of ischemic heart disease cases."
Breast cancer survivors engaging in structured exercise increase the drainage of lymph from their upper limbs, thereby decreasing the side effects of mastectomy, significantly lowering their risk of cancer relapse and improving their immune functions.
Structured exercise improves insulin resistance, reduces hyperinsulinaemia and reduces the risk for diabetes, which could explain the link between increased structured exercise and reduced risk for these cancers.
Recent findings indicate that women with a history of breast cancer who engage in more than 9 metabolic equivalent h/week of structured exercise after a breast cancer diagnosis had a significantly lower risk of death or breast cancer recurrence than women who were physically inactive.
Incubation of MCF-7 estrogen-responsive breast cancer cells and MDA-MB-231 triple-negative breast cancer cells treated with post-exercise serum, from both healthy volunteers and operated cancer patients resulted in a reduction of breast cancer cell viability in comparison with breast cancer cells incubated with pre-exercise sera.
Accordingly, the authors analyzed circulating mi RNAs expression profiles before and after structured exercise and evaluated their potential anti-cancer properties in breast cancer cells.
The Pulliero Research Team concluded in their Oncotarget Research Article, "this study provides evidence that miRNA modulation is a specific molecular mechanism through which structured exercise exerts preventive effects against cancer. The possibility of using these two miRNAs for breast cancer prevention is of interest. MicroRNA as delivered by lipid nanoparticles has been already been effective in mice in preventing NNK induced lung cancer [46]. However, insofar no similar experiments exist as far as concern breast cancer prevention.
Moreover, the evaluation of miR-206 and anti-miR-30c levels in the blood of breast cancer patients could be useful as non-invasive biomarkers in guiding future strategies for cancer prevention."
DOI - https://doi.org/10.18632/oncotarget.27609
Full text - https://www.oncotarget.com/article/27609/text/
Correspondence to - Alessandra Pulliero - alessandra.pulliero@unige.it
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open-access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
PRESS RELEASE https://www.eurekalert.org/pub_releases/2020-05/ijl-aes052720.php#
Volume 11, Number 21 of @Oncotarget reported that eligible patients with stable or responding mPDA after 6 months on chemotherapy were randomized 1:1 to metformin alone or with rapamycin, stratified by prior treatment with FOLFIRINOX. Metformin +/ rapamycin maintenance for mPDA was well-tolerated and several patients achieved stable disease associated with exceptionally long survival.
Dr. Dung T. Le from The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, 21287 said, "Pancreatic ductal adenocarcinoma (PDA) is aggressive cancer with high mortality at all stages and limited treatment options in the advanced setting."
Metformin is an antidiabetic drug in the biguanide class of agents which inhibits mTOR complex 1 primarily through AMP-kinase activation.
A synergistic effect of the combination of metformin with rapamycin was suggested by preclinical studies demonstrating enhanced inhibition of mTOR in a pancreatic cancer cell line and better growth inhibition of pancreatic cancer cells in a xenograft tumor model with the combination than either agent alone.
Based on this, they conducted an exploratory study of metformin with or without rapamycin in patients with mPDA in the maintenance setting.
The Le Research Team concluded in their Oncotarget Research Article, "the administration of metformin with or without rapamycin in patients with mPDA who achieve a response to chemotherapy is well-tolerated and was associated with better than expected overall survival in this study. Additional studies are needed to prospectively evaluate the role of these agents compared to a maintenance chemotherapy or observation only approach."
Sign up for free Altmetric alerts about this article
DOI - https://doi.org/10.18632/oncotarget.27539
Full text - https://www.oncotarget.com/article/27586/text/
Correspondence to - Dung T. Le - dle@jhmi.edu
Keywords - pancreatic cancer, mTOR inhibition, maintenance therapy, metformin
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
Human papillomavirus confers radiosensitivity in oropharyngeal cancer cells
The cover for issue 16 of Oncotarget features Figure 6, "Radiation-induced DNA damage measured by γ-H2AX foci formation at a specified time point after 10 Gy irradiation," by Zhang, et al.
HPV-negative UM-SCC4 with and without transfection of HPV E6 oncoprotein, HPV-negative UPCI-SCC-089, and HPV-positive UPCI-SCC-099 cell lines were used in this study.
The survival fraction after 10 Gy was significantly lower for the HPV-positive SCC-099 cells than for the HPV-negative cells.
In contrast, the HPV-positive UPCI-SCC-099 cells displayed persistent -H2AX activity; the expression of -H2AX remained high at 48 hours post-radiation.
HPV-positive SCC-099 cells were more likely to show the classical apoptotic changes of increased cell thickness and increased motility after radiation.
Dr. Angela Hong from The Faculty of Medicine and Health, Central Clinical School at The University of Sydney as well as The Department of Radiation Oncology, Chris O’Brien Lifehouse said, "Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is clinically and biologically distinct from smoking-related (HPV-negative) OPSCC."
The overall better prognosis seen in HPV-positive OPSCC may be related to the disease's response to radiation therapy.
Radiation therapy plays an important role in the management of OPSCC, either as definitive therapy or as adjuvant therapy after surgery.
Cellular response to radiation treatment can be observed with a label-free dynamic Holo Monitor, which allows non-invasive visualization and live-cell analysis of radiation responses and the migration potential of cancer cells.
The Hong Research Team concluded in their Oncotarget Research Paper that the enhanced cell motility is due to disruption of the actin-membrane interactions by radiation, initiating the membrane blubbing and generating force to enhance cell motility.
In contrast, the HPV-negative UPCI-SCC-089 cells exhibited cell flattening and enlargement, which are the common cytological features of cell cycle blockage.
DOI - https://doi.org/10.18632/oncotarget.27535
Full text - https://www.oncotarget.com/article/27535/text/
Correspondence to - Matthew H. Taylor - taylmatt@ohsu.edu
Keywords - radiosensitivity, oropharyngeal cancer, human papillomavirus, double-strand break, radiobiology
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957x105
The cover for issue 6 of Oncotarget features Figure 3, "The effect of NCs treatments on routine lab results during disease and recovery progress," by Ben-Nun-Shaul, et al.
Numerous previous attempts to develop therapeutic treatments, directed at discreet targets of the sepsis cascade, could not cope with the complex pathophysiology of sepsis and failed.
Studies in a severe rat sepsis model showed that pre-treatment by NCs led to a dramatic increase in survival, from zero to 75%.
Further studies are needed to determine whether when applied after sepsis onset, the NCs still improve outcomes.
Dr. Arieh Eden from the Department of Anesthesiology, Critical Care and Pain Medicine at the Lady Davis Carmel Medical Center in Haifa, Israel said in their Oncotarget Research Paper, "Sepsis affects millions of individuals annually worldwide, with a mortality of greater than 25%" and according to the Cancer | Sepsis Alliance "Having cancer and undergoing certain treatments for cancer, such as chemotherapy, can result in a weakened immune system, putting you at higher risk for developing an infection that could lead to sepsis. Sometimes incorrectly called blood poisoning, sepsis is the body's often deadly response to infection." https://www.sepsis.org/sepsisand/cancer/
It accounts for more than 50% of hospital deaths, with mortality rates of 10 20% for sepsis, 20 40% for severe sepsis, and 40 80% for septic shock.
In the present study, the authors tested the hypothesis, based on their earlier unpublished research, that empty SV40 capsids would improve the outcome of sepsis.
Twenty years ago we established a procedure for the production of empty SV40 capsid, in order to develop a safe gene delivery vector, to be assembled in vitro from empty capsids and plasmid DNA of choice.
The underlying mechanism was up-regulation of Hsp/c70 and induction of the PI3K/Akt survival pathway, both seen exclusively in kidney tissue of NCs treated mice.
That study revealed that SV40 and/or its NCs elicit concurrently opposing pathways: cellular stress response, pro-apoptotic host defense, and Akt-1 survival pathway.
The Eden Research Team concluded in their Oncotarget paper, that these findings, and the dynamic adjustment of the therapeutic pathways to the recovery course, lead them to suggest that the effect of the NCs is tailored both to the type and to the temporal course of the injury, implying a general homeostatic activity.
The homeostatic nature of the NC activity is also manifested in their negligible effect on the normal control rats.
Full text - https://doi.org/10.18632/oncotarget.27448
Correspondence to - Ariella Oppenheim - ariellao@mail.huji.ac.il and Arieh Eden - ganyneden@gmail.com
Keywords - sepsis, empty SV40 capsids, RNAseq, signaling, cellular functions
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open-access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit http://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/onco... Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact media@impactjournals.com 18009220957x105
PRESS RELEASE: Overall survival in patients with lung adenocarcinoma harboring “niche” mutations: an observational study
The cover for issue 5 of Oncotarget features Figure 2, "Survival curves in the KRAS, EGFR, and niche mutations cohorts," by Aramini, et al.
Mutations were observed in all genes studied, except c-MET, DDR2, MAP2K1, and RET.
The multivariable analysis showed that:
Niche mutations had higher mortality than EGFR mutations KRAS mutations had higher mortality than EGFR mutations, and Niche mutations presented similar mortality to KRAS mutations.
Niche mutations exhibited an increased risk of death when compared with EGFR mutations and a similar risk of death when compared with KRAS mutations.
Dr. Beatrice Aramini from the Division of Thoracic Surgery in Department of Medical and Surgical Sciences at the University of Modena and Reggio Emilia in Modena Italy said in their Oncotarget Research Paper, "In the last century, carcinoma of the lung has progressed from an uncommon and obscure disease to the most common cancer in the world, and the most common cause of death from cancer."
In addition to these somatic mutations, which are the most frequent, other mutations in several genes have been discovered, including BRAF, c-MET, DDR2, HER2, MAP2K1, NRAS, PIK3CA, and RET mutations.
Moreover, the prevalence of the RET mutation in adenocarcinoma was estimated to be 1.7%, and the prevalence of DDR2 mutation in lung cancer was 2.2%.
With regard to treatment, discoveries of gene mutations have allowed the development of targeted therapies, which are considered more effective for survival than chemotherapy in patients with advanced mutated disease.
Considering the potential aggressiveness of niche mutations in this context, the technological advances of next-generation sequencing, which is currently used in clinical practice, represents a precise approach to identifying a large panel of mutations in oncologic patients.
The Armini Research Team concluded, "The correct selection of mutations will be helpful in terms of the greater efficacy of treatment in association with better prognosis and a higher quality of life for oncologic patients."
Full text - https://doi.org/10.18632/oncotarget.27472
Correspondence to - Beatrice Aramini,beatrice.aramini@unimore.it
Keywords - somatic mutations, non-small cell lung cancer (NSCLC), lung cancer treatment, overall survival, target therapy
Sign up for free Altmetric alerts about this article
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit http://www.oncotarget.com or connect with:
YouTube - http://bit.ly/OncotargetYoutube SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM
Oncotarget interviews Dr. Beatrice Aramini from the University of Modena and Reggio Emilia in Modena Italy about their Featured Cover Paper for Volume 11 Issue 5 titled "Overall survival in patients with lung adenocarcinoma harboring “niche” mutations: an observational study"
PRESS RELEASE: The cover for issue 5 of Oncotarget features Figure 2, "Survival curves in the KRAS, EGFR, and niche mutations cohorts," by Aramini, et al.
Mutations were observed in all genes studied, except c-MET, DDR2, MAP2K1, and RET.
The multivariable analysis showed that:
Niche mutations had higher mortality than EGFR mutations KRAS mutations had higher mortality than EGFR mutations, and Niche mutations presented similar mortality to KRAS mutations.
Niche mutations exhibited an increased risk of death when compared with EGFR mutations and a similar risk of death when compared with KRAS mutations.
Dr. Beatrice Aramini from the Division of Thoracic Surgery in Department of Medical and Surgical Sciences at the University of Modena and Reggio Emilia in Modena Italy said in their Oncotarget Research Paper, "In the last century, carcinoma of the lung has progressed from an uncommon and obscure disease to the most common cancer in the world, and the most common cause of death from cancer."
In addition to these somatic mutations, which are the most frequent, other mutations in several genes have been discovered, including BRAF, c-MET, DDR2, HER2, MAP2K1, NRAS, PIK3CA, and RET mutations.
Moreover, the prevalence of the RET mutation in adenocarcinoma was estimated to be 1.7%, and the prevalence of DDR2 mutation in lung cancer was 2.2%.
With regard to treatment, discoveries of gene mutations have allowed the development of targeted therapies, which are considered more effective for survival than chemotherapy in patients with advanced mutated disease.
Considering the potential aggressiveness of niche mutations in this context, the technological advances of next-generation sequencing, which is currently used in clinical practice, represents a precise approach to identifying a large panel of mutations in oncologic patients.
The Armini Research Team concluded, "The correct selection of mutations will be helpful in terms of the greater efficacy of treatment in association with better prognosis and a higher quality of life for oncologic patients."
Full text - https://doi.org/10.18632/oncotarget.27472
Correspondence to - Beatrice Aramini,beatrice.aramini@unimore.it
Keywords - somatic mutations, non-small cell lung cancer (NSCLC), lung cancer treatment, overall survival, target therapy
Sign up for free Altmetric alerts about this article
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open-access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit http://www.oncotarget.com or connect with:
YouTube - http://bit.ly/OncotargetYoutube SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM
The cover for issue 68 of Oncotarget features Figure 4, "Gene expression changes to the TME demonstrate sequential development of innate and adaptive immune responses," by Leong, et al.
Intratumoral injection of SD-101 induces significant anti-tumor immunity in preclinical and clinical studies, especially when combined with PD-1 blockade.
Combination therapy generated CD8+ T cell-dependent immunity leading to rejection of both non-injected and injected tumors and long-term survival, even in very large tumors.
Dr. Mary J. Janatpour from Dynavax Technologies, Inc., Emeryville, CA 94608, USA said, "It has long been appreciated by cancer researchers that the phenotypic heterogeneity and progressive evolution of malignant tumors minimize the chance that any agent targeting a single molecular pathway could effectively cure advanced cancer."
The authors have previously demonstrated in mouse tumor models that employing the innate immune system to prime a T cell response, in combination with checkpoint blockade, results in deep and durable anti-tumor efficacy.
These high response rates were observed in both injected and non-injected tumor lesions and patients with PD-L1 negative tumors, indicating low levels of basal immune inflammation, responded as well as patients with PD-L1 positive tumors.
Intratumorally administered SD-101 exerts its priming activity and ultimate orchestration of a systemic anti-tumor T cell response through multiple mechanisms.
The production of interferon stimulates tumor cell killing by natural killer cells, with ensuing tumor antigen release, and induces chemokines that attract T cells back to the tumor bed.
Low-dose cyclophosphamide decreases Tregs. Additional impacted biological activities have been described, such as:
increased interferon production, induction of immunogenic cell death, increases in effector T cells, and increases in functional NK cells,
...likely to be complementary to SD-101 activity by virtue of modulation of the TME. By administering SD-101 locally, rather than systemically, the researchers demonstrate that localized SD-101 injection combined with systemically administered low-dose cyclophosphamide confers an anti-tumor response at non-injected sites.
The Janatpour research Team concluded that taken together, the intratumoral SD-101 plus low-dose CY combination may complement existing checkpoint blockade therapies in patients to improve efficacy in the clinic and extend the benefits of immunotherapy to more patients.
Full text - https://doi.org/10.18632/oncotarget.27322
Correspondence to - Mary J. Janatpour - mjanatpour@dynavax.com
Keywords - TLR9, SD-101, cyclophosphamide, immune therapy, innate immunity
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open-access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit http://www.oncotarget.com or connect with @Oncotarget
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM
Prof. Malka Cohen-Armon and her team at Tel Aviv University's Sackler Faculty of Medicine choose Oncotarget for a third time amongst leading medical journals like The New England Journal of Medicine, Nature or The Lancet to publish groundbreaking preclinical cancer research.
Here's more: Recent reports demonstrate an exclusive eradication of a variety of human cancer cells by the modified phenanthridine PJ34. The efficient eradication of malignant cells in human pancreatic cancer xenografts presents a new model of pancreas cancer treatment.
Prof. Malka Cohen-Armon from the Sackler Faculty of Medicine & the Sagol School of Neuroscience at Tel-Aviv University in Tel-Aviv, Israel said, "Despite a substantial advance in cancer treatment, pancreatic ductal adenocarcinoma (PDAC) have a limited response to current treatments, and a low 5-years survival rate of about 6%."
Furthermore, the authors identified phenanthrenes acting as PARP1 inhibitors that efficiently eradicate a variety of human cancer cells without impairing benign cells.
However, their PARP1 inhibition per-se does not impair nor eradicate human malignant cells, including pancreatic cancer cells, PANC1.
In contrast, at higher concentrations than those causing PARP1 inhibition, PJ34, Tiq-A and Phen eradicate a variety of human cancer cells by mitotic catastrophe cell death.
Here, the efficacy of PJ34 to eradicate human pancreas cancer cells is tested in cell cultures and in xenografts.
In xenografts, eradication of human PANC1 cells deduced from a massive reduction of human proteins in the tumors was measured 30 days after the treatment with PJ34 has been terminated.
The Cohen-Armon Research Team concluded that PJ34, which is permeable in the cell membrane, accessed and eradicated human PDAC cells in xenografts without impairing normal proliferating cells infiltrated into the tumors. The team is 2-3 years away from clinical human trials.
Full text - https://doi.org/10.18632/oncotarget.2...
Correspondence to - Malka Cohen-Armon - marmon@tauex.tau.ac.il
Keywords - PJ34, pancreas cancer, stroma, PANC1 cancer xenografts
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit http://www.oncotarget.com or connect with @Oncotarget
Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact 18009220957x105 MEDIA@IMPACTJOURNALS.COM
The cover for issue 2 of Oncotarget features Figure 5, "MASPIN can prevent the formation of UPA - UPA-receptor complex by a single step, and thus decrease the possibility of the abnormal degradation of the ECM, the development metastasis and angiogenesis," by Fodor, et al.
In the present study, the research team investigated AEZS-108 induced cytotoxicity and the altered mRNA expression profile of regulatory factors related to angiogenesis and metastasis in LHRH receptor-positive OCM3 cells.
Their results show that AEZS-108 upregulates the expression of MASPIN/SERPINB5 tumor suppressor gene, which is downregulated in the normal uvea and UM specimens independently from the LHRH receptor-ligand interaction.
In order to investigate the mechanism of the induction of MASPIN by AEZS-108, OCM3 cells were treated with free DOX, D-Lys6 LHRH analog, or AEZS-108.
Dr. Gabor Halmos from the University of Debrecen, Department of Biopharmacy, in Debrecen, Hungary as well as the Veterans Affairs Medical Center, Endocrine, Polypeptide and Cancer Institute, in Miami, FL, USA said, "Although uveal melanoma (UM) is a rare disease, it is the most prevalent lethal ophthalmological tumor."
The discovery of specific receptors for peptide hormones on cancer cells has led to the development of cytotoxic or radiolabeled hormone analogs that are appropriate for tumor localization and targeted therapy.
AEZS-108 guides the chemotherapeutic agent specifically to those tumors that express LHRH-receptors, which could result in targeted cytotoxicity and less damage to healthy tissues.
The authors reported that previously OCM3 UM cell line expresses the receptor of LHRH localized on the cell membrane and in the cytoplasm, rendering them susceptible to AEZS-108 uptake and the detection of the LHRH receptor in OCM3 cells has led to the use of AEZS-108 for targeted therapy of the tumor.
Moreover, that the OCM3 UM cell line expresses the LHRH receptor and LHRH rendering them susceptible to AEZS-108 uptake.
The Halmos Research Team concluded, "In summary, our data confirmed previous results showing LHRH receptor expression in OCM3 cells, a UM in vitro model. Furthermore, we report for the first time that AEZS-108 causes changes in the expression of genes that are involved in angiogenesis and ECM degradation and which might inhibit cell proliferation and induce apoptosis in OCM3 cells.
These findings suggest that AEZS-108 plays a pivotal role in the regulation of angiogenesis and tumor suppression. Taken together, targeted cytotoxic LHRH analogs, such as AEZS-108, might serve as an effective treatment for patients with LHRH receptor-positive uveal melanoma.”
Keywords - uveal melanoma; luteinizing hormone-releasing hormone (LHRH) receptor; angiogenesis; MASPIN/SERPINB5; AEZS-108 (AN-152/Zoptarelin Doxorubicin Acetate
DOI - https://doi.org/10.18632/oncotarget.27431
Full text - http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=27431&path%5B%5D=89358
Correspondence to - Gabor Halmos, email: halmos.gabor@pharm.unideb.hu
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open-access biomedical journal covering research on all aspects of oncology.
Oncotarget is published by Impact Journals, LLC. To learn more please visit http://www.oncotarget.com or connect with:
Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/
PRESS RELEASE https://www.eurekalert.org/pub_releases/2019-10/ijl-oeb101019.php
The 2019 Nobel Prize in Physiology or Medicine has been awarded jointly to Oncotarget Editorial Board Members William G. Kaelin Jr. and Gregg L. Semenza for their discoveries of "how cells sense and adapt to oxygen availability", said the Nobel Committee. The pair was named alongside the UK physician-scientist Sir Peter J. Ratcliffe.
The Nobel Committee made the announcement Monday at the Karolinska Institute in Stockholm, Sweden and the discoveries have implications for how we understand and potentially treat a range of conditions like cancer, heart attack, stroke and anemia. The Nobel Laureates identified molecular machinery that regulates the activity of genes in response to varying levels of oxygen.
Gregg L. Semenza is a professor of Medicine at Johns Hopkins University and Director of the Vascular Research Program at Johns Hopkins Institute for Cell Engineering. Semenza received the Nobel Prize for the discovery of hypoxia-inducible factor 1 (HIF-1), protein, which controls genes in response to changes in oxygen availability.
William G. Kaelin Jr., a Professor of medicine at Harvard Medical School and the Dana-Farber Cancer Institute, earned his share of the Nobel Prize for his work investigating a genetic syndrome called Von Hippel-Lindau's (VHL) disease. Kaelin discovered that the VHL protein prevents the onset of cancer and is involved in the oxygen sensing mechanism through its interaction with HIF-1.
The awarded mechanism has a fundamental importance in physiology, and has far-reaching implications for the treatment of lw-oxygen health conditions such as coronary artery disease and tumor growth.
Both William G. Kaelin and Gregg L. Semenza are founding members of Oncotarget, launched in 2010. Oncotarget is a weekly peer-reviewed open access bio-medical journal covering research on all aspects of oncology. The editors-in-chief are Mikhail (Misha) Blagosklonny and Andrei V. Gudkov.
About Oncotarget
Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
Oncotarget is published by Impact Journals LLC.
To learn more about Oncotarget, please visit http://www.ImpactJournals.com
Media Contact:
media@oncotarget.com 800.922.0957
"Genomic characterization of metastatic ultra-hypermutated interdigitating dendritic cell sarcoma through rapid research autopsy"
The research team’s analyses revealed ultra-hypermutation, defined as greater than 100 mutations per megabase, in this patients cancer, which was further characterized by the presence of three distinct mutational signatures including UV radiation and APOBEC signatures.
Truncal alterations, defined as being present in all clonal tumor cell populations, in this patients cancer include point mutations in TP53 and CDKN2A and amplifications of c-KIT and APOBEC3A-H, which are likely driver mutations.
Dr. Sameek Roychowdhury from the Department of Internal Medicine, Division of Medical Oncology, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA said, "Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare malignancy of dendritic cell origin with approximately 100 cases reported to date"
Localized IDCS constitutes 47% of cases and manifests as painless lymphadenopathy, most commonly involving the cervical and axillary nodes.
Isolated extra-nodal disease occurs in 25% of cases, involving the liver, lung, spleen, bone marrow and gastrointestinal tract .
Distant metastases occur in 39% of cases and most frequently involved lymph nodes, lung, liver and bone marrow .
Here they performed whole exome sequencing of multiple tumors obtained through rapid research autopsy of a patient with metastatic IDCS. In August 2016, the patient underwent modified radical right neck dissection and partial submandibular gland excision with one level I lymph node demonstrating complete tumor involvement and suspicious for extranodal extension; remaining lymph nodes from levels II, III and IV were negative for tumor infiltration.
In the future, it will be important to study additional patients with this and other rare cancers with hypermutation.
The Roychowdhury research team concluded, “Finally, the broader clinical implication of our results is that although patients with hypermutated cancer, originating from either somatic or germline genomic aberrations, are more likely to benefit from checkpoint inhibition, research is still needed to stratify these patients to maximize therapeutic efficacy and identify the different genetic determinants of primary or acquired resistance to immunotherapy.”
Full text - http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=26352&path%5B%5D=82077
Correspondence to - Sameek Roychowdhury email: Sameek.Roychowdhury@osumc.edu
Keywords - tumor heterogeneity, research autopsy, hypermutation
About Oncotarget
Oncotarget is a twice-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology and publishing sub-sections on topics beyond oncology, including Aging, Immunology and Microbiology, Autophagy, Pathology and Chromosomes among others.
Oncotarget is published by Impact Journals LLC.
To learn more about Oncotarget, please visit http://www.ImpactJournals.com
Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N
Oncotarget Audiopaper - The anti-psychotic drug pimozide is a novel chemotherapeutic for breast cancer
Full text - http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=26175&path%5B%5D=81612
El-Habib Dakir1,2,8, Adam Pickard1, Kirtiman Srivastava1, Cian M. McCrudden3, Stephane R. Gross4, Stephen Lloyd5, Shu-Dong Zhang6, Andriana Margariti7, Richard Morgan8, Philip S. Rudland9 and Mohamed El-Tanani8
1Center for Cancer Research and Cell Biology, Queen’s University, Belfast, UK 2Instituto de Biología Molecular y Celular del Cáncer, Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Salamanca, Salamanca, Spain 3School of Pharmacy, Queen’s University Belfast, Belfast, UK 4School of Life and Health Sciences, Aston University, Birmingham, UK 5School of Medicine, Animal Facility, Queen’s University Belfast, Belfast, UK 6Northern Ireland Centre for Stratified Medicine, Biomedical Sciences, University of Ulster, UK 7Center of Experimental Medicine, Queen’s University Belfast, Belfast, UK 8Institute of Cancer Therapeutics, University of Bradford, Bradford, UK 9Institute of integrative Biology, University of Liverpool, Liverpool, UK Correspondance to:
El-Habib Dakir, email: dakir@usal.es
Mohamed El-Tanani, email: M.El-Tanani@bradford.ac.uk
Oncotarget Interview with Professor Mohamed El-Tanani
Full text - http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=26175&path%5B%5D=81612
El-Habib Dakir1,2,8, Adam Pickard1, Kirtiman Srivastava1, Cian M. McCrudden3, Stephane R. Gross4, Stephen Lloyd5, Shu-Dong Zhang6, Andriana Margariti7, Richard Morgan8, Philip S. Rudland9 and Mohamed El-Tanani8
1Center for Cancer Research and Cell Biology, Queen’s University, Belfast, UK 2Instituto de Biología Molecular y Celular del Cáncer, Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Salamanca, Salamanca, Spain 3School of Pharmacy, Queen’s University Belfast, Belfast, UK 4School of Life and Health Sciences, Aston University, Birmingham, UK 5School of Medicine, Animal Facility, Queen’s University Belfast, Belfast, UK 6Northern Ireland Centre for Stratified Medicine, Biomedical Sciences, University of Ulster, UK 7Center of Experimental Medicine, Queen’s University Belfast, Belfast, UK 8Institute of Cancer Therapeutics, University of Bradford, Bradford, UK 9Institute of integrative Biology, University of Liverpool, Liverpool, UK Correspondance to:
El-Habib Dakir, email: dakir@usal.es
Mohamed El-Tanani, email: M.El-Tanani@bradford.ac.uk
Evaluation of intracavitary administration of curcumin for the treatment of sarcomatoid mesothelioma
http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=15744&path[]=50330
Daniel L. Pouliquen1,2,3, Béatrice Nawrocki-Raby4,5,6, Joëlle Nader1,2,3, Stéphanie Blandin2,7, Myriam Robard2,7, Philippe Birembaut4,5,6,8 and Marc Grégoire1,2,3
1 INSERM, UMR 1232, Nantes, France 2 Université de Nantes, Nantes, France 3 CNRS ERL, Nantes, France 4 INSERM, UMR-S 903, Reims, France 5 Université de Reims Champagne-Ardenne, Reims, France 6 SFR CAP-Santé, Reims, France 7 Plate-forme MicroPICell, SFR François Bonamy, Nantes, France 8 Laboratory of Biopathology, CHU Reims, Reims, France
Correspondence to:
Daniel L. Pouliquen, email: daniel.pouliquen@inserm.fr
https://www.rapamycinpress.com/blog/oncotarget/possible-new-target-breast-cancer-treatment/
Systematic functional perturbations uncover a prognostic genetic network driving human breast cancer
Oncotarget. 2017; 8:20572-20587. https://doi.org/10.18632/oncotarget.16244
Tristan Gallenne1,9, Kenneth N. Ross4,5,, Nils L. Visser1,, Salony4,5,*, Christophe J. Desmet1, Ben S. Wittner4,5, Lodewyk F.A. Wessels2,3, Sridhar Ramaswamy4,5,6,7,8 and Daniel S. Peeper1
1 Department of Molecular Oncology, The Netherlands Cancer Institute, Plesmanlaan, CX, Amsterdam, The Netherlands 2 Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, Plesmanlaan, CX, Amsterdam, The Netherlands 3 Faculty of EEMCS Delft University of Technology, Delft, The Netherlands 4 Massachusetts General Hospital Cancer Center, Boston, MA, USA 5 Harvard Medical School, Boston, MA, USA 6 Broad Institute of Harvard & MIT, Cambridge, MA, USA 7 Harvard Stem Cell Institute, Cambridge, MA, USA 8 Harvard-Ludwig Center for Cancer Research, Boston, MA, USA 9 Current address: Merus B.V., Padualaan, CH Utrecht, The Netherlands * These authors have contributed equally
Correspondence to:
Sridhar Ramaswamy, email: sridhar@mgh.harvard.edu
Daniel S. Peeper, email: d.peeper@nki.nl
Keywords: breast cancer, metastasis, prognosis, tumor biology
Received: December 14, 2016 Accepted: January 28, 2017 Published: March 15, 2017
http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=16244&path[]=51959
Full Text - http://bit.ly/2EJcb1k
Interview with Francisco Esteva, Adriana Heguy, and Alireza Khodadadi-Jamayran about their paper "Prognostic role of elevated mir-24-3p in breast cancer and its association with the metastatic process."
Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N
www.Oncotarget.com
Full Text - http://bit.ly/2F4cBLS
Ovarian cancer is the most lethal of gynecologic cancers in the United States resulting in 14.000 deaths each year. The majority of ovarian cancer arises from fallopian tube or ovarian surface epithelial cells. Despite major differences in the features, all ovarian cancers are treated with surgery followed by chemotherapy.
Facebook - bit.ly/2xznxjV Twitter - bit.ly/2xzWvsu LinkedIn - bit.ly/2xzJ6kc Pintrest - bit.ly/2xzX8SS Reddit - bit.ly/2hoxI0N
Full Text - http://bit.ly/2HDDBn2
The mechanism called nucleotide excision repair (NER), responsible for protecting our skin and organs from the effects of carcinogens and UV radiation, is poorly understood. In Oncotarget, Volume 8, Issue 57, researchers set out to understand the specific role a gene protein called ubiquitin-specific peptidase 11 (USP11) plays in suppressing DNA damage and the development of tumors.
Facebook - bit.ly/2xznxjV Twitter - bit.ly/2xzWvsu LinkedIn - bit.ly/2xzJ6kc Pintrest - bit.ly/2xzX8SS Reddit - bit.ly/2hoxI0N
Link to YouTube video - http://bit.ly/2HyQX43
Link to Full Text - http://bit.ly/2BDp3U6
Oncotarget | Interview with Dr. Ken Pienta and Dr. Jim Frost of Johns Hopkins School of Medicine talking about their experience publishing "Symmetry and symmetry breaking in cancer: a foundational approach to the cancer problem."
Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N
www.Oncotarget.com
Full Text - http://bit.ly/2odFHlK
Rapamycin Press recently interviewed Dr. J. James Frost, M.D., Ph.D., M.B.A. to discuss his collaborative research paper “Symmetry and Symmetry Breaking in Cancer: A Foundational Approach to the Cancer Problem.”
Facebook - bit.ly/2xznxjV Twitter - bit.ly/2xzWvsu LinkedIn - bit.ly/2xzJ6kc Pintrest - bit.ly/2xzX8SS Reddit - bit.ly/2hoxI0N
www.Oncotarget.com
Full Text - http://bit.ly/2BD4M0Y
A slight change in a protein can cause prostate cancer cells to become aggressive and invade other parts of the body, a new study found. The research findings, which were published in Oncotarget, provide more insight into the aggressive nature of cancer and could lead to the development of more effective treatments.
Facebook - bit.ly/2xznxjV Twitter - bit.ly/2xzWvsu LinkedIn - bit.ly/2xzJ6kc Pintrest - bit.ly/2xzX8SS Reddit - bit.ly/2hoxI0N
Full Text- http://bit.ly/2DnHaPQ
We, the scientists, should change the situation and change the policies of Indexes such as Clarivate's Web of Science, and Medline, and make indexes work for us. Otherwise, why should all of these organizations exist?
Facebook - bit.ly/2xznxjV Twitter - bit.ly/2xzWvsu LinkedIn - bit.ly/2xzJ6kc Pintrest - bit.ly/2xzX8SS Reddit - bit.ly/2hoxI0N
www.Oncotarget.com
Symmetry and symmetry breaking in cancer: a foundational approach to the cancer problem
https://tinyurl.com/yab9jbxb
Symmetry and symmetry breaking concepts from physics and biology are applied to the problem of cancer. Three categories of symmetry breaking in cancer are examined: combinatorial, geometric, and functional. Within these categories, symmetry breaking is examined for relevant cancer features, including epithelial-mesenchymal transition (EMT); tumor heterogeneity; tensegrity; fractal geometric and information structure; functional interaction networks; and network stabilizability and attack tolerance. The new cancer symmetry concepts are relevant to homeostasis loss in cancer and to its origin, spread, treatment and resistance. Symmetry and symmetry breaking could provide a new way of thinking and a pathway to a solution of the cancer problem.
Facebook - bit.ly/2xznxjV Twitter - bit.ly/2xzWvsu LinkedIn - bit.ly/2xzJ6kc Pintrest - bit.ly/2xzX8SS Reddit - bit.ly/2hoxI0N
www.Oncotarget.com
Effective control of acute myeloid leukaemia and acute lymphoblastic leukaemia progression by telomerase specific adoptive T-cell therapy
Full Text- https://tinyurl.com/yb3gjwqs
Telomerase (TERT) is a ribonucleoprotein enzyme that preserves the molecular organization at the ends of eukaryotic chromosomes. Since TERT deregulation is a common step in leukaemia, treatments targeting telomerase might be useful for the therapy of hematologic malignancies. Despite a large spectrum of potential drugs, their bench-to-bedside translation is quite limited, with only a therapeutic vaccine in the clinic and a telomerase inhibitor at late stage of preclinical validation. We recently demonstrated that the adoptive transfer of T cell transduced with an HLA-A2-restricted T-cell receptor (TCR), which recognize human TERT with high avidity, controls human B-cell chronic lymphocytic leukaemia (B-CLL) progression without severe side-effects in humanized mice. In the present report, we show the ability of our approach to limit the progression of more aggressive leukemic pathologies, such as acute myeloid leukaemia (AML) and B-cell acute lymphoblastic leukaemia (B-ALL). Together, our findings demonstrate that TERT-based adoptive cell therapy is a concrete platform of T cell-mediated immunotherapy for leukaemia treatment.
Facebook - bit.ly/2xznxjV Twitter - bit.ly/2xzWvsu LinkedIn - bit.ly/2xzJ6kc Pintrest - bit.ly/2xzX8SS Reddit - bit.ly/2hoxI0N
www.Oncotarget.com
Full Text- https://tinyurl.com/yavmxbxt
The genetic heterogeneity of acute myeloid leukemia (AML) and the variable responses of individual patients to therapy suggest that different AML genotypes may influence the bone marrow (BM) microenvironment in different ways. We performed gene expression profiling of bone marrow mesenchymal stromal cells (BM-MSC) isolated from normal C57BL/6 mice or mice inoculated with syngeneic murine leukemia cells carrying different human AML genotypes, developed in mice with Trp53 wild-type or nullgenetic backgrounds. We identified a set of genes whose expression in BM-MSC was modulated by all four AML genotypes tested. In addition, there were sets of differentially-expressed genes in AML-exposed BM-MSC that were unique to the particular AML genotype or Trp53 status. Our findings support the hypothesis that leukemia cells alter the transcriptome of surrounding BM stromal cells, in both common and genotype-specific ways. These changes are likely to be advantageous to AML cells, affecting disease progression and response to chemotherapy, and suggest opportunities for stroma-targeting therapy, including those based on AML genotype.
Facebook - bit.ly/2xznxjV Twitter - bit.ly/2xzWvsu LinkedIn - bit.ly/2xzJ6kc Pintrest - bit.ly/2xzX8SS Reddit - bit.ly/2hoxI0N www.Oncotarget.com
Full text- https://tinyurl.com/yde6fsk7
Significant limitations exist in our ability to predict breast cancer risk at the individual level. Circulating microRNAs (C-miRNAs) have emerged as measurable biomarkers (liquid biopsies) for cancer detection. We evaluated the ability of C-miRNAs to identify women most likely to develop breast cancer by profiling miRNA from serum obtained long before diagnosis. 24 breast cancer cases and controls (matched for risk and age) were identified from women enrolled in the High-Risk Breast Program at the UVM Cancer Center. Isolated RNA from serum was profiled for over 2500 human miRNAs. The miRNA expression data were input into a stepwise linear regression model to discover a multivariable miRNA signature that predicts long-term risk of breast cancer. 25 candidate miRNAs were identified that individually classified cases and controls based on statistical methodologies. A refined 6-miRNA risk-signature was discovered following regression modeling that distinguishes cases and controls (AUC0.896, CI 0.804-0.988) in this cohort. A functional relationship between miRNAs that cluster together when cases are contrasted against controls was suggested and confirmed by pathway analyses. The discovered 6 miRNA risk-signature can discriminate high-risk women who ultimately develop breast cancer from those who remain cancer-free, improving current risk assessment models. Future studies will focus on functional analysis of the miRNAs in this signature and testing in larger cohorts. We propose that the combined signature is highly significant for predicting cancer risk, and worthy of further screening in larger, independent clinical cohorts.
Facebook - bit.ly/2xznxjV Twitter - bit.ly/2xzWvsu LinkedIn - bit.ly/2xzJ6kc Pintrest - bit.ly/2xzX8SS Reddit - bit.ly/2hoxI0N
Full text - http://bit.ly/2mGYI1J
Oncotarget | Interview with Dr. Marene Landstrom & Dr. Reshma Sundar with the Department of Medical Biosciences, Umeå University Sweden talking about their experience publishing "Pro-invasive properties of Snail1 are regulated by sumoylation in response to TGFβ stimulation in prostate cancer"
Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N
www.Oncotarget.com
Full text - http://bit.ly/2mlYU6k
"ERβ inhibits cyclin dependent kinases 1 and 7 in triple negative breast cancer"
Abstract - Triple negative breast cancer (TNBC), which comprises approximately 15% of all primary breast cancer diagnoses, lacks estrogen receptor alpha, progesterone receptor and human epidermal growth factor receptor 2 expression. However, we, and others, have demonstrated that approximately 30% of TNBCs express estrogen receptor beta (ERβ), a nuclear hormone receptor and potential drug target. Treatment of ERβ expressing MDA-MB-231 cells with estrogen or the ERβ selective agonist, LY500307, was shown to result in suppression of cell proliferation. This inhibitory effect was due to blockade of cell cycle progression. In vivo, estrogen treatment significantly repressed the growth of ERβ expressing MDA-MB-231 cell line xenografts. Gene expression studies and ingenuity pathway analysis identified a network of ERβ down-regulated genes involved in cell cycle progression including CDK1, cyclin B and cyclin H. siRNA mediated knockdown or drug inhibition of CDK1 and CDK7 in TNBC cells resulted in substantial decreases in proliferation regardless of ERβ expression. These data suggest that the tumor suppressive effects of ERβ in TNBC result from inhibition of cell cycle progression, effects that are in part mediated by suppression of CDK1/7. Furthermore, these data indicate that blockade of CDK1/7 activity in TNBC may be of therapeutic benefit, an area of study that has yet to be explored.
Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N
www.Oncotarget.com
Full text - bit.ly/2mlYU6k
Interview with Dr. John R. Hawse from the Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA talking about their paper "ERβ inhibits cyclin dependent kinases 1 and 7 in triple negative breast cancer"
Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N
www.Oncotarget.com
Title - Screening of cancer tissue arrays identifies CXCR4 on adrenocortical carcinoma: correlates with expression and quantification on metastases using 64Cu-plerixafor PET
Abstract - Expression of the chemokine receptor CXCR4 by many cancers correlates with aggressive clinical behavior. As part of the initial studies in a project whose goal was to quantify CXCR4 expression on cancers non-invasively, we examined CXCR4 expression in cancer samples by immunohistochemistry using a validated anti-CXCR4 antibody. Among solid tumors, we found expression of CXCR4 on significant percentages of major types of kidney, lung, and pancreatic adenocarcinomas, and, notably, on metastases of clear cell renal cell carcinoma and squamous cell carcinoma of the lung. We found particularly high expression of CXCR4 on adrenocortical cancer (ACC) metastases. Microarrays of ACC metastases revealed correlations between expression of CXCR4 and other chemokine system genes, particularly CXCR7/ACKR3, which encodes an atypical chemokine receptor that shares a ligand, CXCL12, with CXCR4. A first-in-human study using 64Cu-plerixafor for PET in an ACC patient prior to resection of metastases showed heterogeneity among metastatic nodules and good correlations among PET SUVs, CXCR4 staining, and CXCR4 mRNA. Additionally, we were able to show that CXCR4 expression correlated with the rates of growth of the pulmonary lesions in this patient. Further studies are needed to understand better the role of CXCR4 in ACC and whether targeting it may be beneficial. In this regard, non-invasive methods for assessing CXCR4 expression, such as PET using 64Cu-plerixafor, should be important investigative tools.
Full text - http://bit.ly/2hwPKOq
Facebook - bit.ly/2xznxjV Twitter - bit.ly/2xzWvsu LinkedIn - bit.ly/2xzJ6kc Pintrest - bit.ly/2xzX8SS Reddit - bit.ly/2hoxI0N
www.Oncotarget.com
The Featured Cover Paper for the most recent issue of @Oncotarget -http://bit.ly/2yG5wlh
A Priority Research Paper by Pongas, et al. titled “PI3Kδ inhibition causes feedback activation of PI3Kα in the ABC subtype of diffuse large B-cell lymphoma”
The corresponding author is Dr. Louis M. Staudt from the Lymphoid Malignancies Branch of the National Cancer Institute at National Institutes of Health in Bethesda, MD, USA.
Please share your thoughts or ask questions about the research on our Facebook page.
Full text - http://bit.ly/28Ncmoy
Oncotarget | Interview with Dr. René Bernards & Diede Brunen - Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, The Netherlands - talking about their cover paper published in Volume 7 Issue 25 of Oncotarget called "Intrinsic resistance to PIM kinase inhibition in AML through p38α-mediated feedback activation of mTOR signaling"
Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N
www.Oncotarget.com
Full text - http://bit.ly/2ocULhq
Interview with Dr. Raz with the Department of Orthopaedics, Leiden University Medical Center, in the Leiden Netherlands talking about their featured cover paper in Oncotarget Volume 7 Number 8 "Molecular signatures of age-associated chronic degeneration of shoulder muscles"
Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N
www.Oncotarget.com
Full text - http://bit.ly/1TYK5Rg
Oncotarget | Interview with Dr. Markus D. Siegelin & Dr. Georg Karpel-Massler - Department of Pathology & Cell Biology, Columbia University Medical Center, New York, New York, U.S.A. talking about their cover paper published in Volume 7 Issue 23 of Oncotarget called "Metabolic reprogramming of glioblastoma cells by L-asparaginase sensitizes for apoptosis in vitro and in vivo"
Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N
www.Oncotarget.com
Full text - http://bit.ly/2pgqWjW
Oncotarget | Interview with Dr. Kelber from the Department of Biology, California State University Northridge, Northridge, CA talking about their featured cover paper in Oncotarget Volume 8 Issue 4 "A novel method for RNA extraction from FFPE samples reveals significant differences in biomarker expression between orthotopic and subcutaneous pancreatic cancer patient-derived xenografts"
Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N
www.Oncotarget.com
Full text - http://bit.ly/2duVAwX
Oncotarget | Interview with Dr. Joyce Schroeder - Professor Molecular & Cellular Biology and BIO5 Institute Chief Scientific Officer at the Arizona Cancer Therapeutics Carcinogenesis Department of Molecular and Cellular Biology University of Arizona, Tucson, Arizona speaking about their Cover Paper in Oncotarget Volume 7 Issue 38 "Llgl1 prevents metaplastic survival driven by epidermal growth factor dependent migration"
Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N
www.Oncotarget.com
Full text - http://bit.ly/2yVSSPa
Oncotarget | Interview with Dr. Jaclyn Hechtman from the Department of Pathology Memorial Sloan Kettering Cancer Center, New York, NY, USAtalking about their Cover paper - Volume 7 Issue 32 - Oncotarget -"Recurrent, truncating SOX9 mutations are associated with SOX9 overexpression, KRAS mutation, and TP53 wild type status in colorectal carcinoma"
Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N
www.Oncotarget.com
Full text - http://bit.ly/2yTX4uJ
Oncotarget | Interview with Dr. Gregory J. Riggins from the Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, MD, USA talking about their featured cover paper published in Volume 8 Issue 46 titled "Synergistic and targeted therapy with a procaspase-3 activator and temozolomide extends survival in glioma rodent models and is feasible for the treatment of canine malignant glioma patients".
Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N
www.Oncotarget.com
Full text - http://bit.ly/2xAJ4bQ
Oncotarget | Interview with Dr. Fon Tacer from the Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA (currently with St. Judes Children's Hospital, Department of Cell and Molecular Biology in Tennessee, USA) talking about their research in Volume 7 Issue 3 titled "γKlotho is a novel marker and cell survival factor in a subset of triple negative breast cancers"
Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N
www.Oncotarget.com
Full text - http://bit.ly/2hTOg0O
Oncotarget | Interview with Dr. Dmitrovsky from the University of Texas MD Anderson Cancer Center, Houston, TX talking about their featured cover paper in Oncotarget Volume 8 Issue 1 "The ISG15-specific protease USP18 regulates stability of PTEN"
Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N
www.Oncotarget.com
Full text - http://bit.ly/2yWQ6Jx
Oncotarget | Interview with Dr. Bruno Larrivee from Departments of Biomedical Sciences, Molecular Biology and Ophthalmology - Maisonneuve-Rosemont Hospital Research Center, University of Montreal, Montreal, Quebec, Canada & Department of Biological Sciences Université du Québec à Montréal, Montréal, Quebec, Canada talking about their featured cover paper in Oncotarget Volume 7 Issue 35 "BMP9/ALK1 inhibits neovascularization in mouse models of age-related macular degeneration"
Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N
www.Oncotarget.com
Full text - http://bit.ly/2hqMzYN
Oncotarget | Interview with Dr. Anutosh Ganguly from the Department of Integrative Biology and Pharmacology, University of Texas Medical School, 6431 Fannin St., Houston, Texas 77030, USA talking about their research published in Volume 2 Issue 5 titled "Class III β-Tubulin Counteracts the Ability of Paclitaxel to Inhibit Cell Migration"
Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N
www.Oncotarget.com
Full text - http://bit.ly/2hR9kW0
Oncotarget | Interview with Dr. Hirbe from the Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA talking about their featured cover paper in Oncotarget Volume 7 Issue 7 “Spatially- and temporally-controlled postnatal p53 knockdown cooperates with embryonic Schwann cell precursor Nf1 gene loss to promote malignant peripheral nerve sheath tumor formation”
Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N
www.Oncotarget.com
Full Text: bit.ly/2xufwZQ
Critically, our findings suggest for the first time that targeting BRAFWT/V600E and CDK4/6 represents a novel therapeutic strategy to treat vemurafenib-resistant or vemurafenib-naïve radioiodine-refractory BRAFWT/V600E-PTC. This combined therapy could prevent selection and expansion of aggressive PTC cell sub-clones with intrinsic resistance, targeting tumor cells either with primary or secondary resistance to BRAFV600E inhibitor.
Facebook - bit.ly/2xznxjV Twitter - bit.ly/2xzWvsu LinkedIn - bit.ly/2xzJ6kc Pintrest - bit.ly/2xzX8SS Reddit - bit.ly/2hoxI0N
www.Oncotarget.com
Audiopaper - Published in Volume 8 Issue 42 of Oncotarget - "A global comparison of the cost of patented cancer drugs in relation to global differences in wealth" by Daniel A. Goldstein from the Davidoff Cancer Center, Rabin Medical Center, Petach Tikvah, Israel and the Winship Cancer Institute, Emory University, Atlanta, GA, USA
Full text - http://bit.ly/2xBGMsU
Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N
www.Oncotarget.com
Sustained autophagy contributes to the metabolic adaptation of cancer cells to hypoxic and acidic microenvironments. Since cells in such environments are resistant to conventional cytotoxic drugs, inhibition of autophagy represents a promising therapeutic strategy in clinical oncology. We previously reported that the efficacy of hydroxychloroquine (HCQ), an autophagy inhibitor under clinical investigation is strongly impaired in acidic tumor environments, due to poor uptake of the drug, a phenomenon widely associated with drug resistance towards many weak bases. In this study we identified salinomycin (SAL) as a potent inhibitor of autophagy and cytotoxic agent effective on several cancer cell lines under conditions of transient and chronic acidosis. Since SAL has been reported to specifically target cancer-stem cells (CSC), we used an established model of breast CSC and CSC derived from breast cancer patients to examine whether this specificity may be associated with autophagy inhibition. We indeed found that CSC-like cells are more sensitive to autophagy inhibition compared to cells not expressing CSC markers. We also report that the ability of SAL to inhibit mammosphere formation from CSC-like cells was dramatically enhanced in acidic conditions. We propose that the development and use of clinically suitable SAL derivatives may result in improved autophagy inhibition in cancer cells and CSC in the acidic tumor microenvironment and lead to clinical benefits.
Full text - http://bit.ly/2m8L2Mk
Facebook - bit.ly/2xznxjV Twitter - bit.ly/2xzWvsu LinkedIn - bit.ly/2xzJ6kc Pintrest - bit.ly/2xzX8SS Reddit - bit.ly/2hoxI0N
www.Oncotarget.com