Agents that target androgen synthesis in castration-resistant prostate cancer

Abstract

In April 2011, abiraterone acetate (in combination with low-dose steroids) was approved by the US Food and Drug Administration for the treatment of men with metastatic, castration-resistant prostate cancer who have previously been treated with docetaxel-based chemotherapy. The development of abiraterone was the successful result of an improved understanding of the role of the androgen receptor signaling pathway in castration-resistant prostate cancer. Abiraterone is a rationally designed potent inhibitor of cytochrome P450, family 17, subfamily A, polypeptide 1, which is essential for synthesis of testosterone from nongonadal precursors. More recently, other drugs that act along the androgen0synthesis pathway, such as orteronel (TAK-700) and galeterone (TOK-001), have shown promise in early clinical trials. Here, we review the discovery and clinical development of abiraterone and other novel androgen-synthesis inhibitors for the management of advanced prostate cancer.