Targeting the androgen receptor signalling axis in castration-resistant prostate cancer (CRPC)

Despite undergoing local therapy with curative intent, 20-30% of patients with prostate cancer will ultimately development metastatic disease, leading to morbidity and mortality. Androgen-deprivation therapy (ADT) for men with metastatic prostate cancer results in transient clinical benefit, but ultimately, cancers progress despite castrate levels of serum testosterone, a clinical state classically referred to as 'hormone refractory' disease. In this review, we examine mechanisms of resistance to ADT that have redefined our understanding of the more appropriately termed 'castration resistant' disease, and have paved the way for a new generation of therapeutics targeting the androgen signalling axis in advanced prostate cancer.