Mechanisms and targeting of proteosome-dependent androgen receptor degradation in prostate cancer.

The androgen receptor (AR) remains to be a key target for the treatment of prostate cancer, including the majority of castration-resistant prostate cancer (CRPC). AR is stabilized in CRPC and the ubiquitin-proteasome system (UPS) plays a major role in AR degradation. Targeting AR for degradation provides a potential approach to overcome the resistance of CRPC to current AR antagonists, including the next generation AR signaling inhibitors. Different types of AR degraders have been developed, including the proteolysis-targeting chimeras (PROTACs), selective AR degraders (SARDs), and novel AR degraders, with several AR PROTACs currently in clinical trials. The present mini-review discusses the regulation of AR degradation by the UPS, the potential role of a novel nuclear degradation signal in AR, and different types of AR degraders.