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Although a succession of randomised controlled trials have improved outcomes across all stages of disease, there remain significant clinical challenges and unmet needs. Repurposed drugs have attracted interest in the treatment of prostate cancer, where a number of agents have been proposed with a range of mechanisms of action suggesting potential benefits. A major advantage of such drugs is the wealth of pre-existing patient safety data typically available, meaning repurposed agents would be expected to have a known and often low toxicity profile and also (as often late in their developmental pathway and hence generic drugs are available) attractive in terms of cost effectiveness. The evidence required for repurposed drugs to become accepted standards of care and enter the treatment formulary however is no less arduous than conventional development pathways, where confirmatory results from randomised phase III trials remain the absolute requirement. Additionally, these efforts are often led by academic trial groups \u2013 with challenges then in the steps to licensing that are typically undertaken by industry. To date, despite large scale initiatives, there is a paucity of drugs successfully repurposed in this way. Using examples across the different clinical scenarios we discuss the opportunities and challenges, design and analyses of current phase III trials testing repurposed drugs for the treatment of patients with prostate cancer and highlight where future success may come.<\/jats:p>","DOI":"10.1186\/s40360-025-01077-w","type":"journal-article","created":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T08:36:08Z","timestamp":1769243768000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Drug re-purposing to improve outcomes in the management of prostate cancer \u2013 aims, outcome measures and design of current phase III trials"],"prefix":"10.1186","volume":"27","author":[{"given":"Duncan C.","family":"Gilbert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth E.","family":"Langley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dami","family":"Ayadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mannab","family":"Berhanu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmi Kowdley","family":"Hemanth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seunghee","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossameldin","family":"Abdallah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Meade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Gillessen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"James","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gauthier","family":"Bouche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahesh","family":"Parmar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Nankivell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,24]]},"reference":[{"key":"1077_CR1","unstructured":"Cancer Research UK. 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NC is supported by research funds GU Cancer Research, Christie and Salford Royal Hospitals NHS Foundation Trusts, Prostate Cancer UK and the Prostate Cancer Foundation. SG: SG reports personal fees from Tolremo, Ipsen, and Avalere Health; and speakers fees and travel support from AstraZeneca, Bayer, Intellisphere LLC, Gilead, Silvio Grasso Consulting, WebMD-Medscape, Peer Voice, European Society for Medical Oncology, American Society of Clinical Oncology Genitourinary Cancers Symposium, Deutschsprachingen Europ\u00e4ischen Schule f\u00fcr Onkologie (DESO), AdMeTech Foundation, EPG Health, Meister Concept GmbH, and Swiss Group for Clinical Cancer Research (SAKK); advisory or leadership roles at Telixpharma, Novartis, Modra Pharmaceuticals, Orion, Bayer, AstraZeneca, Myriad Genetic, Amgen, MSD, Bristol-Myers Squibb, Daiichi Sankyo, Boehringer Ingelheim, Innomedica, Macrogenics, Astells, and Pfizer; and co-inventor on patent application (WO 2009138392 A1) for \u201ca method for biomarker discovery\u201d (granted in China, Europe, Japan, and USA) outside the submitted work. NDJ: reports having received direct support from the Institute of Cancer Research and having received research grants and personal fees from AstraZeneca, Janssen, Astellas and Novartis; personal fees from Bayer, Clovis, Merck Sharp & Dohme, Sanofi; and advisory roles for AstraZeneca, Bayer, Clovis, Janssen, Merck, Novartis, Sanofi, and Gilead, and for AAA Accelerator Systems as part of the VISION trial Independent Data Monitoring Committee, outside the submitted work. MKBP: reports educational grants and non-financial support to the Clinical Trials Unit from Novartis, Pfizer, ROCHE, ROCHE Products, Sanofi, Serum Institute of India, Shionogi, SUMVAX, Synteny Biotechnology, Takeda, Tibotec, Transgene, ViiV Healthcare, Virco Xenothera, CSL Behring, Eli-Lilly, Emergent Biosolutions, Gilead Sciences, GlaxoSmithKline, Grifols, ICON, Janssen Products LP, Janssen-Cilag, Janssen Pharmaceutica, Johnson & Johnson, Merck Serono, Micronoma, Modus Theraputics, MSD, Mylan, Abcodia Pvt Ltd, Advanced Accelerator \u2013 Applications International SA, Akagera, Amgen, Aspirin Foundation, Astellas, AstraZeneca, AoA, Baxter, Bayer, Bristol Myers Squibb US, Brii Biosciences, B&C Group, Cepheid, Cipla, and Clovis, outside the submitted work. LMu: reports having received grants from Cancer Research UK, and from Janssen, Astellas, Novartis, Sanofi, and Clovis as part of the wider STAMPEDE trial for the duration of this study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"35"}}