Updates on therapeutic targets and agents in castration-resistant prostate cancer

Prostate cancer (PCa) is the most commonly diagnosed noncutaneous cancer in men accounting for 28% of all newly diagnosed cancer cases and it is the second to third most common cause of cancer death in the Western world. Nearly all patients with metastatic disease will eventually experience disease progression despite castration as the median duration of response is between 18-24 months. Hence, development of castration-resistant prostate cancer (CRPC) is only a matter of time in these patients. CRPC is defined by disease progression despite androgen-deprivation therapy. CRPC presents a spectrum of disease ranging from rising PSA levels to metastases and significant debilitation from cancer symptoms. Prognosis is associated with several factors, including performance status, presence of bone pain, extent of disease on bone scan, and serum levels of alkaline phosphatase. Based on our enhanced understanding of tumor biology, including the role of tumor, host, and hormonal signaling, there has been rational development of new therapies for CRPC. Over the last decade, several clinical trials have been launched to study novel agents targeting different mechanisms of PCa progression, and have culminated success of new agents for CRPC (docetaxel, cabazitaxel, sipuleucel-T, denosumab, and abiraterone acetate) and several more molecules are on the horizon. The purpose of this review is to discuss the new therapeutic targets in CRPC focusing on new promising agents.