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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.<\/jats:p>","DOI":"10.1177\/17588359261424672","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T06:53:03Z","timestamp":1773471183000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Antibody-drug conjugates in prostate cancer: current landscape and future directions"],"prefix":"10.1177","volume":"18","author":[{"given":"Zeynep Irem","family":"Ozay","sequence":"first","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chadi","family":"Hage Chehade","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Gebrael","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micah","family":"Ostrowski","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Sayegh","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT"},{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umang","family":"Swami","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeraj","family":"Agarwal","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21871"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2023.06.009"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djz035"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-19-0582"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2022.07.009"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.0532"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.00646"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15041278"},{"key":"e_1_3_3_10_2","unstructured":"Agarwal N. 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