{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:56:26Z","timestamp":1790182586891,"version":"4.1.0"},"reference-count":220,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Inhibiting the activity of the androgen receptor (AR) is the cornerstone treatment for advanced prostate cancer. AR-targeted therapies are highly effective in slowing disease progression but are not curative. Failure of these therapies results in a disease state termed castration-resistant prostate cancer, which is associated with significant patient morbidity and mortality. In most cases, resistance to AR-targeted therapies arises due to alterations that reactivate the AR signalling axis. Interestingly, it has long been recognised that potent activation of AR with supraphysiological levels of androgens can suppress prostate cancer growth in both preclinical models and patients. This intriguing paradox, where both inhibition and activation of AR have anti-cancer effects, is now being harnessed clinically in the form of bipolar androgen therapy (BAT). This review describes mechanisms underlying the tumour-suppressive functions of AR in the context of potent androgenic stimulation and discusses how our maturing understanding of these processes is influencing the clinical deployment of BAT.<\/jats:p>","DOI":"10.1530\/erc-24-0208","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T07:52:00Z","timestamp":1731052320000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":4,"title":["Friend or foe? Deciphering androgen receptor action to improve bipolar androgen therapy for prostate cancer"],"prefix":"10.1530","volume":"32","author":[{"given":"Samuel P G","family":"Rollin","sequence":"first","affiliation":[{"name":"Flinders University, College of Medicine and Public Health, Flinders Health and Medical Research Institute 1 , , ,","place":["Bedford Park, South Australia, Australia"]},{"name":"Flinders University, Freemasons Centre for Male Health and Wellbeing 2 , , ,","place":["Bedford Park, South Australia, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell G","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University 3 , , ,","place":["Clayton, Victoria, Australia"]},{"name":"The Sir Peter MacCallum Department of Oncology, University of Melbourne 4 , , Victoria,","place":["Parkville, Australia"]},{"name":"Peter MacCallum Cancer Centre 5 , , ,","place":["Melbourne, Victoria, Australia"]},{"name":"Cabrini Institute, Cabrini Health 6 , , ,","place":["Malvern, Victoria, Australia"]},{"name":"Melbourne Urological Research Alliance (MURAL), Monash Biomedicine Discovery Institute Cancer Program, Monash University 7 , , ,","place":["Clayton, Victoria, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony M","family":"Joshua","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health Network 8 , ,","place":["Toronto, Canada"]},{"name":"Kinghorn Cancer Centre, St Vincent\u2019s Hospital, Garvan Institute of Medical Research 9 , , New South Wales,","place":["Sydney, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4686-1418","authenticated-orcid":true,"given":"Luke A","family":"Selth","sequence":"additional","affiliation":[{"name":"Flinders University, College of Medicine and Public Health, Flinders Health and Medical Research Institute 1 , , ,","place":["Bedford Park, South Australia, Australia"]},{"name":"Flinders University, Freemasons Centre for Male Health and Wellbeing 2 , , ,","place":["Bedford Park, South Australia, Australia"]},{"name":"Faculty of Health and Medical Sciences, University of Adelaide 10 , , South Australia,","place":["Adelaide, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2024,11,8]]},"reference":[{"key":"2026070905402284700_bib2","doi-asserted-by":"crossref","first-page":"102725","DOI":"10.1016\/j.jbc.2022.102725","article-title":"Biphasic transcriptional and posttranscriptional regulation of MYB by androgen signaling mediates its growth control in prostate cancer","volume":"299","author":"Acharya","year":"2023","journal-title":"J Biol Chem"},{"key":"2026070905402284700_bib3","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1158\/2767-9764.CRC-21-0139","article-title":"Potent stimulation of the androgen receptor instigates a viral mimicry response in prostate cancer","volume":"2","author":"Alizadeh-Ghodsi","year":"2022","journal-title":"Cancer Res Commun"},{"key":"2026070905402284700_bib4","doi-asserted-by":"crossref","first-page":"216468","DOI":"10.1016\/j.canlet.2023.216468","article-title":"Androgen receptor inhibition suppresses anti-tumor neutrophil response against bone metastatic prostate cancer via regulation of T\u03b2RI expression","volume":"579","author":"Alsamraae","year":"2023","journal-title":"Cancer Lett"},{"key":"2026070905402284700_bib5","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.3389\/fimmu.2020.01647","article-title":"Supraphysiological levels of testosterone induce vascular dysfunction via activation of the NLRP3 inflammasome","volume":"11","author":"Alves","year":"2020","journal-title":"Front Immunol"},{"key":"2026070905402284700_bib6","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1002\/pros.22828","article-title":"Androgen receptor (AR) suppresses normal human prostate epithelial cell proliferation via AR\/\u03b2-catenin\/TCF-4 complex inhibition of c-MYC transcription","volume":"74","author":"Antony","year":"2014","journal-title":"Prostate"},{"key":"2026070905402284700_bib7","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1038\/nrurol.2011.107","article-title":"Time to stratify? 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