How to cite: Yu EY. “Novel Targeted Treatments for Metastatic Prostate Cancer.” Grand Rounds in Urology. October 25, 2025. Accessed Oct 2026. https://grandroundsinurology.com/novel-targeted-treatments-for-metastatic-prostate-cancer/
Summary
Evan Y. Yu, MD, Professor of Oncology, University of Washington, Seattle, Washington, reviews novel targeted treatment strategies for prostate cancer beyond androgen receptor and prostate-specific membrane antigen (PSMA)-directed therapies. Dr. Yu provides an in-depth overview of emerging cell surface and intracellular targets reshaping the therapeutic landscape for advanced disease.
Cell surface targets including STEAP1, KLK2, TROP2, B7H3, CD46, and DLL3 are discussed in detail. Dr. Yu emphasizes that early failures often reflected poor drug constructs rather than invalid targets. Newer bispecific antibodies and antibody drug conjugates demonstrate improved efficacy and safety profiles. STEAP1 and KLK2 CD3 bispecific antibodies show encouraging prostate-specific antigen (PSA) and radiographic responses, while B7H3 and CD46 antibody drug conjugates are advancing into randomized trials.
Neuroendocrine prostate cancer remains a major unmet need. DLL3-directed trispecific T-cell engagers demonstrate early activity in selected patients and represent one of the most promising strategies in this aggressive disease subtype.
Dr. Yu also explores non–cell surface targeting strategies, focusing on EZH2 inhibition. Phase II data with mevrometostat combined with enzalutamide show improvements in radiographic progression-free survival, objective response rates, and PSA responses, leading to ongoing phase III trials.
Dr. Yu highlights how advances in immunotherapy engineering, payload design, and molecular selection are enabling a new generation of targeted treatments for prostate cancer.
About the 28th Annual Southwest Prostate Cancer Symposium:
Presented by Program Chairs Nelson N. Stone, MD, Richard G. Stock, MD, and William K. Oh, MD, this conference educated attendees about advances in the management of localized and advanced prostate cancer, with a focus on imaging, technology, and training in the related devices. It included a scientific session, as well as live demonstrations of surgical techniques. You can learn more about the conference here.
ABOUT THE AUTHOR
Evan Y. Yu, MD, is a medical oncologist specializing in prostate, bladder, and testicular cancer treatment and research. He graduated Alpha Omega Alpha from the University of Washington School of Medicine. He completed internal medicine residency at the Brigham and Women’s Hospital and oncology fellowship and post-doctoral training at the Dana-Farber Cancer Institute. He returned to Seattle at the end of 2004 to join the faculty at the University of Washington and Fred Hutchinson Cancer Research Center. He now is a Full Professor, the Clinical Research Director for GU malignancies, Core Director for the Pacific Northwest Prostate Cancer SPORE and co-PI of the DoD Prostate Cancer Clinical Trials Consortium at his institution. His research focuses on testing the next wave of novel molecular targeted therapies and immunotherapy techniques, with a complementary focus on imaging biomarkers. In addition to an active clinical and research practice, he also is the Medical Director for Clinical Research Services at the Fred Hutchinson Cancer Consortium. He served as a Hematology/Oncology Fellowship Program Director for a decade at the Fred Hutchinson Cancer Research Center. He has regularly been voted a “Top Doctor” by Castle Connolly, U.S. News and World Report, Seattle magazine, and Seattle Met magazine. He has served for many years on the National Cancer Institute Genitourinary Cancers Steering Committee and is newly appointed as the Co-Chair for the National Cancer Institute Prostate Cancer Task Force. He remains active in SWOG and he also serves as an editor for Clinical Cancer Research, Clinical Genitourinary Cancer, and Uro-Today.
