{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:10:07Z","timestamp":1789650607617,"version":"4.0.0"},"reference-count":23,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100019756","name":"Kaohsiung Municipal Siaogang Hospital","doi-asserted-by":"publisher","award":["S\u2010114\u201004"],"award-info":[{"award-number":["S\u2010114\u201004"]}],"id":[{"id":"10.13039\/100019756","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Prostate cancer remains a leading cause of cancer\u2010related mortality, largely driven by progression to metastatic castration\u2010resistant prostate cancer (mCRPC). Although poly(ADP\u2010ribose) polymerase inhibitors (PARPis) have improved outcomes in patients with homologous recombination repair (HRR) alterations, particularly in\n                    <jats:italic>BRCA2<\/jats:italic>\n                    \u2010mutated disease, their clinical benefit is limited by restricted patient selection, modest efficacy in non\u2010\n                    <jats:italic>BRCA<\/jats:italic>\n                    HRR alterations, and the frequent emergence of resistance. These limitations highlight an unmet need for strategies that can both expand the therapeutic population and overcome PARPi resistance. Bipolar androgen therapy (BAT), which alternates between supraphysiological and near\u2010castrate androgen exposure, has emerged as a paradoxical yet clinically active approach in mCRPC. Unlike conventional androgen deprivation strategies, preclinical evidence suggests that BAT induces acute androgen receptor\u2013mediated DNA damage while simultaneously suppressing HRR gene expression. This dual effect may generate a transcription\u2010coupled homologous recombination\u2013deficient state that is independent of canonical baseline genomic HRR alterations, thereby potentially sensitizing tumors to PARP inhibition. Current clinical trials of BAT combined with PARP inhibitors suggest activity in both HRR\u2010deficient and HRR\u2010proficient disease. Collectively, these findings suggest a preliminary, hypothesis\u2010generating conceptual framework in which BAT may expand the therapeutic scope of PARPis beyond genomically defined HRR\u2010mutated tumors and may help counteract mechanisms of PARPi resistance in mCRPC.\n                  <\/jats:p>","DOI":"10.1002\/kjm2.70292","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:30:54Z","timestamp":1789648254000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bipolar Androgen Therapy as a Potential Mechanistic Bridge to Enhance\n                    <scp>PARP<\/scp>\n                    Inhibitor Efficacy in Prostate Cancer"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3239-0712","authenticated-orcid":false,"given":"Jhen\u2010Hao","family":"Jhan","sequence":"first","affiliation":[{"name":"Department of Urology Brigham and Women's Hospital &amp; Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Urology Kaohsiung Municipal Siaogang Hospital  Kaohsiung Taiwan"},{"name":"Department of Urology Kaohsiung Medical University Hospital  Kaohsiung Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Department of Urology, School of Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0610-1278","authenticated-orcid":false,"given":"Jiun\u2010Hung","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Urology Brigham and Women's Hospital &amp; Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Urology Kaohsiung Municipal Siaogang Hospital  Kaohsiung Taiwan"},{"name":"Department of Urology Kaohsiung Medical University Hospital  Kaohsiung Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Department of Urology, School of Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4208-3858","authenticated-orcid":false,"given":"Hung\u2010Lung","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Urology Kaohsiung Medical University Hospital  Kaohsiung Taiwan"},{"name":"Department of Urology Kaohsiung Medical University Gangshan Hospital  Kaohsiung Taiwan"},{"name":"School of Post\u2010Baccalaureate Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2968-6125","authenticated-orcid":false,"given":"Shu\u2010Pin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Urology Kaohsiung Medical University Hospital  Kaohsiung Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Institute of Medical Science and Technology, College of Medicine National Sun Yat\u2010Sen University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4017-1157","authenticated-orcid":false,"given":"Li","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Urology Brigham and Women's Hospital &amp; Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a030361"},{"issue":"9","key":"e_1_2_5_3_1","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.trecan.2024.06.008","article-title":"PARPi, BRCA, and Gaps: Controversies and Future Research","volume":"10","author":"Dibitetto D.","year":"2024","journal-title":"Trends Cancer"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2200043"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.10.015"},{"issue":"23","key":"e_1_2_5_6_1","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2426743122","article-title":"BRCA2 Reversion Mutation\u2010Independent Resistance to PARP Inhibition Through Impaired DNA Prereplication Complex Function","volume":"122","author":"Pappas K.","year":"2025","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"e_1_2_5_7_1","doi-asserted-by":"crossref","DOI":"10.1200\/PO-25-00922","article-title":"Advancing Poly (ADP\u2010Ribose) Polymerase Inhibition Strategies Beyond BRCA1\/2 in Prostate Cancer","volume":"9","author":"Jhan J. 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A.","year":"2026","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"}],"container-title":["The Kaohsiung Journal of Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/kjm2.70292","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/kjm2.70292","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/kjm2.70292","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:30:56Z","timestamp":1789648256000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/kjm2.70292"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":23,"alternative-id":["10.1002\/kjm2.70292"],"URL":"https:\/\/doi.org\/10.1002\/kjm2.70292","archive":["Portico"],"relation":{},"ISSN":["1607-551X","2410-8650"],"issn-type":[{"value":"1607-551X","type":"print"},{"value":"2410-8650","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]},"assertion":[{"value":"2026-05-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70292"}}