Resistance to chemical castration: Second-line hormonal treatment

Although advanced prostate cancer is sensitive to androgen deprivation therapy, the disease finally becomes resistant and progresses into a state called “castration-resistant prostate cancer” which is currently incurable. Several options are available including secondary hormonal manipulations since androgen receptor pathway remains the main oncogenic driver in this setting. Hormonal manipulations include androgen inhibitor withdrawal, the use estrogen therapy, or ketoconazole. More recently, studies on new drugs targeting either adrenal secretion of androgen (such as abiraterone acetate) or second-generation androgen receptor inhibitor (such as MDV3100) showed meaningful clinical benefit for patients with metastatic CRPC. Many other drugs are under preclinical and clinical investigations to better understand their role in the treatment of CRPC.