Laura A Sena, Rajendra Kumar, David E Sanin, Elizabeth A Thompson, D Marc Rosen, Susan L Dalrymple, Lizamma Antony, Yuhan Yang, Carolina Gomes-Alexandre, Jessica L Hicks, Tracy Jones, Kiara A Bowers, Jillian N Eskra, Jennifer Meyers, Anuj Gupta, Alyza Skaist, Srinivasan Yegnasubramanian, Jun Luo, W Nathaniel Brennen, Sushant K Kachhap, Emmanuel S Antonarakis, Angelo M De Marzo, John T Isaacs, Mark C Markowski, Samuel R Denmeade
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...
December 1, 2022: Journal of Clinical Investigation