Phase I and II therapies targeting the androgen receptor for the treatment of castration resistant prostate cancer

Introduction: Prostate cancer is the most common cancer in elderly males. Regardless of the initial hormonal treatment in metastatic disease, a significant proportion of patients develop castration resistant prostate cancer (CRPC). A better understanding of the molecular mechanisms behind castration resistance has led to the approval of oral medications such as abiraterone acetate and enzalutamide. Relevant research is accelerated with numerous agents being tested for the management of CRPC. Areas covered: The authors present Phase I and II studies targeting the androgen receptor for the treatment of CRPC. Three groups of agents are identified according to the mechanism of action. These include the CYP-17 modulators (Orteronel, Galeterone, VT-464 and CFG-920), novel antiandrogens (Apatorsen, ARN-509, ODM-201, EZN-4176, AZD-3514) and bipolar androgen therapy. Expert opinion: Further understanding of the mechanisms leading to castration resistance in prostate cancer can reveal potential targets for the development of novel anti-cancer agents. Except for the development of novel antiandrogens and CYP-17 modulators, bipolar androgen therapy is an interesting therapeutic approach. The combinations of the novel agents tested in Phase I and II studies with established agents is another field of interest. The real challenge is to distinguish a novel anti-cancer agent with acceptable tolerability and the best outcome.