biostudies-literatureQiu Xthe Donahue Family Fundthe H.L. Snyder Medical Research FoundationThe Prostate Cancer Foundationthe Institute for Prostate Cancer Researchthe Cutler Family Fund for Prevention and Early DetectionThe Fonds de Recherche du Québec – SantéCanadian Institutes of Healththe Mayer FoundationCraig Watjen Memorial FundsNIHRebecca and Nathan Milikowsky FundCIHRthe Safeway FoundationU.S. Department of Defense Prostate Cancer Research ProgramnciNCIDoris Duke Charitable FoundationNCI NIH HHSClaudia Adams Barr Program for Innovative Cancer ResearchProstate Cancer FoundationNIGMS NIH HHSNIH HHSe157164https://www.ebi.ac.uk/biostudies/studies/S-EPMC9220831biostudies-literatureUnknown7(10)The androgen receptor (AR) is a master transcription factor that regulates prostate cancer (PC) development and progression. Inhibition of AR signaling by androgen deprivation is the first-line therapy with initial efficacy for advanced and recurrent PC. Paradoxically, supraphysiological levels of testosterone (SPT) also inhibit PC progression. However, as with any therapy, not all patients show a therapeutic benefit, and responses differ widely in magnitude and duration. In this study, we evaluated whether differences in the AR cistrome before treatment can distinguish between SPT-responding (R) and -nonresponding (NR) tumors. We provide the first preclinical evidence to our knowledge that SPT-R tumors exhibit a distinct AR cistrome when compared with SPT-NR tumors, indicating a differentJCI insightResponse to supraphysiological testosterone is predicted by a distinct androgen receptor cistrome.PMC9220831D.P.L. is a Lewis Katz – Young Investigator of the Prostate Cancer FoundationP01 CA163227RebeccaNathan Milikowsky Fundthe Mayer FoundationCraig Watjen Memorial FundsR01 CA251555Early DetectionP01CA163227R01GM107427,R01CA193910,R01CA251555,R01CA234715R21CA194798S10 OD028685R01 CA193910Claudia Adams Barr Program for Innovative Cancer ResearchW81XWH-20-1-0111,W81XWH-21-1-0229,W81XWH-19-1-0565,W81XWH-18-1-0347,W81XWH-18-1-0354the Cutler Family Fund for PreventionD.P.L. is a Research Scholar – Junior 1PNW Prostate Cancer SPORE P50CA097186the Donahue Family FundGrant 2021184the H.L. Snyder Medical Research FoundationThe Prostate Cancer FoundationR01 GM107427the Institute for Prostate Cancer ResearchP50 CA097186the Safeway FoundationR01 CA234715S10OD028685R21 CA194798PJT-162246Pomerantz MSeo JHBell CHanratty BBoufaied NFeng FYAbou Alaiwi SFreedman MLQiu XLong HWBrown MHaffner MCNguyen HMBrown LGConner JLLabbe DPNelson PSO'Connor EEl Zarif TCorey EfalseResponse to supraphysiological testosterone is predicted by a distinct androgen receptor cistrome.The androgen receptor (AR) is a master transcription factor that regulates prostate cancer (PC) development and progression. Inhibition of AR signaling by androgen deprivation is the first-line therapy with initial efficacy for advanced and recurrent PC. Paradoxically, supraphysiological levels of testosterone (SPT) also inhibit PC progression. However, as with any therapy, not all patients show a therapeutic benefit, and responses differ widely in magnitude and duration. In this study, we evaluated whether differences in the AR cistrome before treatment can distinguish between SPT-responding (R) and -nonresponding (NR) tumors. We provide the first preclinical evidence to our knowledge that SPT-R tumors exhibit a distinct AR cistrome when compared with SPT-NR tumors, indicating a different2022-01-01T00:00:00Z2022 May2026-03-31T11:54:27.256Z2025-04-20T03:06:54.892ZS-EPMC92208313560378710.1172/jci.insight.157164