Androgen receptor targeted therapies in metastatic castration-resistant prostate cancer – The urologists' perspective

Abstract

Androgen deprivation therapy (ADT), which involves the maximal suppression of circulating testosterone, underpins the treatment approach to metastatic hormone sensitive prostate cancer. Although initial responses are generally favourable, approximately half of cases progress to metastatic castrate resistant prostate cancer (mCRPC), rendering traditional hormonal therapies ineffective. mCRPC is defined by disease progression despite established ADT. New research has improved our understanding of the the molecular mechanisms behind metastatic castration-resistant prostate cancer (mCRPC). This has led to a renewed interest in the androgen receptor as a target for therapy, paving the way for the introduction of novel androgen therapies such as abiraterone acetate and enzalutamide. Recent trials on these treatments have demonstrated their benefit to improving overall survival in the setting of mCRPC. The resultant effect is a new, constantly changing, and complex treatment paradigm for treating clinicians, who are now required to know the mechanism of actions of new medications, side effect profiles, modes of administration, and preferred sequencing of various treatment options. Furthermore, treatments involving new androgen biosynthesis are currently being developed and tested. Therefore, in the context of a highly heterogenous disease with a continuously changing treatment landscape, management of mCRPC can be particularly challenging. The purpose of this review is to provide an overview of the literature on new androgen receptor targeted therapies, and discuss the changing treatment landscape specific to metastatic CRPC.

Keywords

• Castration-resistant prostate cancer
• Prostate cancer
• Androgen receptor
• Androgen synthesis inhibitor
• Androgen deprivation therapy
• Novel androgen receptor antagonist
• Abiraterone
• Enzalutamide