Androgen receptor activity in prostate cancer dictates efficacy of bipolar androgen therapy through MYC.

ABSTRACT: Testosterone is the canonical growth factor of prostate cancer but can paradoxically suppress its growth when present at supraphysiological levels. We have previously demonstrated that the cyclical administration of supraphysiological androgen (SPA), termed bipolar androgen therapy (BAT), can result in tumor regression and clinical benefit for patients with castration-resistant prostate cancer. However, predictors and mechanisms of response and resistance have been ill defined. Here, we show that growth inhibition of prostate cancer models by SPA required high androgen receptor (AR) activity and were driven in part by downregulation of MYC. Using matched sequential patient biopsies, we show that high pretreatment AR activity predicted downregulation of MYC, improved clinical response, and

SUBMITTER: Sena LA 

PROVIDER: S-EPMC9711876 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature