A New Old Target: Androgen Receptor Signaling and Advanced Prostate Cancer

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.

Automated summary

In the last two decades, there has been significant progress in the treatment of advanced prostate cancer by targeting androgen and the androgen receptor (AR). However, drug resistance remains a challenge that needs to be addressed for the development of future therapeutic strategies.