Chapter 10 Biological targets and new drug development for prostate cancer

Abstract • Androgen receptor (AR) signalling is usually necessary for the development and progression of prostate cancer• Androgen depletion is the mainstay of treatment for advanced prostate cancer but responses can be short-lived• AR-signalling frequently remains intact as prostate cancer evolves from androgen sensitive to castration resistant disease (CRPC)• A number of mechanisms may facilitate AR reactivation, including AR overexpression, AR mutation leading to promiscuous ligand binding or constitutive activation, adrenal and intratumoral androgen synthesis, and activated signal transduction pathways• The AR signalling pathway remains a rational therapeutic target in CRPC.