Owing to the development of multiple novel therapies, there has been major progress in the treatment of advanced prostate cancer over the last two decades; however, the disease remains invariably fatal. Androgens and the androgen receptor (AR) play a critical role in prostate carcinogenesis, and targeting the AR signaling axis with abiraterone, enzalutamide, darolutamide, and apalutamide has improved outcomes for men with this lethal disease. Targeting the AR and elucidating mechanisms of resistance to these agents remain central to drug development efforts. This review provides an overview of the evolution and current approaches for targeting the AR in advanced prostate cancer. It describes the biology of AR signaling, explores AR-targeting resistance mechanisms, and discusses future perspectives and promising novel therapeutic strategies.
Annual review of pharmacology and toxicology. 2021 Aug 24 [Epub]
Daniel Westaby, Maria de Los Dolores Fenor de La Maza, Alec Paschalis, Juan M Jimenez-Vacas, Jon Welti, Johann de Bono, Adam Sharp
The Institute of Cancer Research, London SM2 5NG, United Kingdom; email: .