Androgen action and metabolism in prostate cancer

► Despite castration, prostate cancer remains driven by the androgen receptor (AR) signaling axis. ► Mechanisms of resistance include tumor androgen synthesis and constitutively active AR variants. ► Novel agents targeting ligand synthesis and AR activation have demonstrated striking responses. ► Biomarkers for rational stratification of men to optimal treatment strategies are required. ► The AR axis remains the most attractive therapeutic target for advanced prostate cancer.