Oncotarget

Prostate cancer remains a significant health concern, especially in advanced stages. Researchers are investigating innovative strategies to combat treatment-resistant forms of the disease. One promising approach involves targeting the androgen receptor's interaction with proliferating cell nuclear antigen. New peptide and small molecule strategies could potentially improve treatment outcomes for patients suffering from castration-resistant prostate cancer. This breakthrough could change the landscape of prostate cancer therapies.

Recent groundbreaking research has uncovered genetic alterations in over 90% of advanced solid tumors, offering new hope for personalized cancer treatments. The analysis of 10,000 tumor samples revealed that nearly a third showed mutations tied to existing drugs. Notably, many critical mutations were detected at low levels, often overlooked by simpler tests. The findings emphasize the vital role of comprehensive genomic profiling in expanding treatment options and improving patient care in various cancer types.

Explore a groundbreaking case report on a unique treatment for advanced pancreatic cancer. A patient using extracorporeal blood filtration showed remarkable clinical improvements, experiencing reduced pain and no new tumor growth over a year. The innovative Seraph® 100 device targets circulating tumor cells, believed to spread cancer. This approach raises exciting possibilities but also highlights the need for more research to validate these early findings.

Discover how cholesterol-lowering statins may play a surprising role in combating colorectal cancer. The discussion reveals exciting research showing these common drugs disrupt the Wnt/β-catenin signaling pathway, which is crucial for tumor growth. Researchers confirmed that statins not only reduce tumor growth but also do so with minimal side effects. This innovative approach could pave the way for repurposing statins in cancer therapy and prevention, offering hope against one of the leading cancer fatalities worldwide.

Dive into the fascinating world of microRNAs and their emerging role in soft tissue sarcomas! Learn how these tiny molecules can serve as non-invasive biomarkers for diagnosing and monitoring cancer. The podcast reveals how microRNAs influence tumor growth and treatment responses, highlighting their potential for personalized medicine. Discover the challenges of translating this knowledge into clinical applications and innovative strategies to harness microRNAs for effective cancer care.

Researchers explore a groundbreaking monoclonal antibody, 2B010, aimed at targeting regulatory T cells in tumors. By selectively depleting these immune suppressors, the treatment enhances anti-tumor responses. Interestingly, it maintains essential immune functions, unlike traditional methods. This innovative approach shows promise for developing new cancer therapies that could empower the body's ability to fight cancer more effectively.

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 Treatment Chemotherapy 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 Cells The 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.28720 Correspondence to - Dindial Ramotar - dramotar@hbku.edu.qa Video short - https://www.youtube.com/watch?v=suOhF7mPlNQ Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28720 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, redox signaling, homologous recombination, protein interaction, cell cycle, protein modification 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/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/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@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.28750 Correspondence to - Noel A. Warfel - warfelna@arizona.edu, and Shailender S. Chauhan - shailenderc@arizona.edu Video short - https://www.youtube.com/watch?v=xFypDT4ALmc Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28750 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, hypoxia, lipid droplets, ferroptosis, resistance, prostate 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/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/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@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.28747 Correspondence to - Susan E. Waltz - susan.waltz@uc.edu, and Vinita Takiar - takiarva@ucmail.uc.edu Video short - https://www.youtube.com/watch?v=RD2W-F3_aX4 About Oncotarget: Website - https://www.oncotarget.com 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/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

Discover the latest breakthroughs in understanding a rare and aggressive blood cancer. The discussion focuses on key genetic mutations like TET2 and ASXL1, which are linked to poorer survival rates, especially in older adults. Learn about the potential of CCDC50 as a valuable biomarker for diagnosis and disease monitoring. This research could pave the way for improved detection and treatment strategies, making a difference in the lives of patients with Blastic Plasmacytoid Dendritic Cell Neoplasm.