Resistance mechanisms of AR-targeted therapy
Several mechanisms facilitate the progression of hormone-sensitive prostate cancer to castration-resistant prostate cancer (CRPC). At present, the approved agents that target androgen signaling, including enzalutamide, abiraterone, apalutamide and darolutamide. Over time, however, all patients inevitably develop resistance to treatment and their disease will continue to progress. In this talk, I will present several key mechanisms that give rise to drug resistance including expression of constitutively active variants of the androgen receptor, such as AR-V7; and intracrine androgens and overexpression of androgen synthesis enzymes like AKR1C3. Treatment strategies are being developed to target these pathways and reintroduce drug sensitivity. By better understanding the mechanisms by which drug resistance develops, improved treatment strategies will be made possible.