Antibody-drug conjugates (ADCs) have emerged as a promising therapeutic option, combining the specificity of monoclonal antibodies with the potency of cytotoxic payloads. While initially developed for hematologic and select solid malignancies, advances in antigen discovery, linker chemistry, and payload design have expanded their application to metastatic castration-resistant prostate cancer, where treatment options remain limited. Prostate-specific membrane antigen (PSMA), STEAP-1, TROP-2, CD46, Nectin-4, tissue factor, B7-H3, and DLL3 have emerged as clinically relevant targets, with multiple ADCs evaluated in early and late-phase trials. Although early-generation drugs were hindered by modest efficacy and significant toxicity due to linker instability and off-target effects, some novel ADCs have shown improved tolerability and encouraging antitumor activity. Ongoing studies are exploring rational combinations with hormonal, other targeted, and immune-based therapies to enhance efficacy, overcome resistance, and expand the role of ADCs in advanced prostate cancer. Herein, we provide a comprehensive overview of the clinical development of ADCs in advanced prostate cancer.
Emerging treatment options in prostate cancer: Antibody-drug conjugates Antibody-drug conjugates (ADCs) are a new type of cancer treatment designed to deliver chemotherapy directly to cancer cells. Each ADC has two parts: an antibody that seeks out a marker on cancer cells, and a chemotherapy attached to it. This design allows tumors to be targeted more precisely while limiting damage to healthy cells. ADCs are now being tested in advanced prostate cancer that no longer responds to hormone therapy, a stage where treatment options are limited. Several tumor markers are being studied as targets for these medicines in clinical trials. Newer ADCs, and combinations with hormone therapy, targeted drugs, and immunotherapy, are also being explored to improve effectiveness and overcome resistance.
Therapeutic advances in medical oncology. 2026 Mar 13*** epublish ***
Zeynep Irem Ozay, Chadi Hage Chehade, Georges Gebrael, Micah Ostrowski, Nicolas Sayegh, Umang Swami, Neeraj Agarwal
Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT., Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope Drive Suite 5510, Salt Lake City, UT 84112, USA.