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.28707 Correspondence to - Wafik S. El-Deiry - wafik@brown.edu Video short - https://www.youtube.com/watch?v=Q_mXy8mana0 Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28707 Subscribe 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/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

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.

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.

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.

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

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/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

Dr. Wade T. Iams, a researcher from the Vanderbilt Ingram Cancer Society Center, dives into the complexities of lung cancer treatment. He discusses a groundbreaking case where a patient developed resistance to lorlatinib due to a rare genetic alteration, RUFY1-RET. This revelation emphasizes the critical role of advanced genetic testing and the necessity for personalized cancer treatments. As cancer evolves, understanding resistance mechanisms becomes vital for effective precision oncology.

New insights challenge traditional approaches to breast cancer treatment. It’s revealed that some early-stage diagnoses may not require immediate surgery, thanks to findings from the COMET trial. This research suggests that active monitoring could be a viable alternative for many patients. The discussion emphasizes the importance of identifying precise biomarkers to ensure only those who truly need intervention receive it. It raises critical questions about the effectiveness of current screening programs in discerning dangerous cancers from those that may never pose a threat.