Attacking the androgen receptor pathway in prostate cancer

Since the 1940’s the androgen receptor has been the main target for systemic therapy in prostate cancer. Classic hormonal therapy aims to lower serum testosterone levels or block the androgen receptor ligand-binding domain. Despite disease progression, castration-resistant prostate cancer remains predominantly androgen-driven as novel secondary hormonal therapy with abiraterone acetate or enzalutamide has demonstrated increased overall survival. Promising androgen synthesis inhibitors (orteronel, galeterone), androgen receptor inhibitors (ARN-509, EPI-001, AZD3514) and heat-shock protein modulators are under investigation. Given the upcoming arsenal of systemic therapies and the molecular heterogeneity of castration-resistant prostate cancer, patient-tailored therapy strategies are being explored.