Abiraterone acetate in castration-resistant prostate cancer

The palliative goal of the treatment of metastatic prostate cancer is to prolong survival and decrease cancer-related complications. Androgen ablation therapy is widely accepted as the initial treatment of choice; when the disease becomes resistant to castration-resistant prostate cancer (CRPC), docetaxel-based chemotherapy aids in prolonging overall survival and controlling disease-related symptoms. Until a few years ago, no drug had showed efficacy in docetaxel-resistant patients. Recently, cabazitaxel, a taxane family compound, has been shown to help prolong survival in patients previously treated with docetaxel, even if a high grade of myelotoxicity has been reported. Moreover, a better understanding of the biology of CRPC has demonstrated that prostate cancer proliferation is largely mediated through the androgen receptor, which could be reactivated by androgens produced by the adrenal glands. Abiraterone acetate is an orally active acetate salt of the steroidal compound abiraterone with antiandrogen activity. Abiraterone inhibits the enzymatic activity of steroid 17α-monooxygenase, a member of the cytochrome P450 family that catalyzes the 17α-hydroxylation of steroid intermediates involved in testosterone synthesis from the adrenal glands. This review focuses on abiraterone acetate, the first compound that, through the inhibition of adrenal gland production of testosterone, increases the overall survival in CRPC patients. The role of possible predictive biomarkers and future perspectives are also discussed.