Oncotarget

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.28711 Correspondence to: Abhijit Basu — abhijit.basu@alumni.uni-ulm.de Video short - https://www.youtube.com/watch?v=G2Tq4_r6xLw Subscribe 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/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

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 Osteosarcoma Osteosarcoma 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.28688 Correspondence to - Antonin Marchais - antonin.marchais@gustaveroussy.fr, and Maria Eugenia Marques Da Costa - jenny.marquescosta@gustaveroussy.fr Video short - https://www.youtube.com/watch?v=f9WgaDoEubs Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28688 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, SETDB1, cancer epigenetics, tumor immunogenicity, mesenchymal differentiation in osteosarcoma 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/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 how artificial intelligence is revolutionizing liver cancer detection! Experts discuss a groundbreaking approach that measures AI's own uncertainty, helping clinicians identify potential issues in medical imaging. This innovative method enhances the accuracy of liver and bile duct scans, making it easier to spot difficult-to-detect tumors. A highlight is the advanced AHUNet model, which confidently analyzes both 2D and 3D images, improving early diagnosis and reducing missed cases.

A groundbreaking study reveals a promising triple therapy for glioblastoma, combining new imipridones with traditional treatments. This innovative approach significantly slows tumor growth and extends survival in mouse models. Researchers are excited about the potential to improve outcomes for patients facing this aggressive brain cancer. The synergy between the new drugs and existing therapies opens up new possibilities in treatment, challenging the limitations of current glioblastoma care.

A groundbreaking discovery reveals the FGR protein's surprising ability to help leukemia cells mature, echoing the effects of retinoic acid therapy. Traditionally seen as a cancer promoter, FGR's new role opens exciting possibilities for treating acute myeloid leukemia. The research shows that simply introducing FGR prompts the cells to produce key maturation markers and shifts their behavior. This innovative finding could pave the way for novel therapies, especially for cases resistant to conventional treatments.

A young woman triumphs over leukemia, only to be confronted with another blood cancer stemming from her bone marrow transplant. This rare case raises crucial questions about the long-term risks of donor cells and the importance of rigorous donor screening. Experts discuss the complexity of hematopoietic stem cell transplants and the unexpected emergence of donor cell–derived hematologic neoplasms. The conversation sheds light on the delicate balance between life-saving treatments and potential long-term complications.

Explore the intriguing role of the NSD2 gene in maintaining the identity of multiple myeloma cells as plasma cells. Researchers delve into how NSD2 influences gene activity, offering new perspectives on treatment for high-risk t(4;14) myeloma. They compare myeloma cells with varying NSD2 activity and uncover significant changes in DNA folding and gene expression. This groundbreaking study could lead to innovative strategies for tackling this challenging form of blood cancer.

Discover why some breast cancer treatments stop working and the critical role of signaling pathways. Researchers reveal how mutations and altered cell communication support tumor survival and resistance. Key pathways like PI3K/Akt/mTOR and HER2 are discussed, shedding light on their impact on treatment response. The insights aim to enhance understanding and pave the way for novel therapeutic strategies. Tune in for an eye-opening exploration of the challenges in treating this prevalent cancer!

Discover the surprising truth about cancer treatment outcomes. Experts reveal that clear scan results can mask hidden cancer, leading to worse long-term effects. They emphasize the need for advanced follow-up techniques, as many patients with clear scans may still harbor microscopic disease. The discussion sheds light on the significant discrepancies between imaging results and tissue analysis, urging a reevaluation of how treatment success is judged. Stay informed about the hidden risks in cancer care that could change survival rates!

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.28703 Correspondence to - Wafik S. El-Deiry - wafik@brown.edu Video short - https://www.youtube.com/watch?v=XAdYfFoMvUM 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. MEDIA@IMPACTJOURNALS.COM