Current state of castration-resistant prostate cancer.

Prostate cancer (PrCa) is the most common cancer found among men in the United States, and is the second-leading cause of death for these individuals. Although most patients with prostate cancer experience disease control after primary therapy, approximately 20% to 40% of these patients will eventually encounter recurrent disease. While androgen deprivation therapy may achieve temporary tumor control or regression in the majority of patients with advanced disease, virtually all patients with metastatic disease will experience progressive PrCa. Consequently, their disease may no longer respond to primary androgen blockade and may then spread to distant sites, most commonly to the bones and/or regional lymph nodes. This state of disease, termed castration-resistant prostate cancer (CRPC), is heterogeneous, has a variety of clinical symptoms which may include biochemical progression, progression in bone, or soft tissue, and may present with or without symptoms from cancer. While treatments were previously somewhat limited, there has been a substantial increase in the understanding of the biological and genetic basis for PrCa progression. The mechanisms of androgen independence in CRPC include, but are not limited to, autocrine production of androgen by the prostate cancer cell, as well as androgen receptor activity despite low testosterone levels, through a variety of different mechanisms. These findings have led to more targeted therapies for CRPC, improved clinical outcomes, and increased survival. Further understanding of the mechanisms that cause castration resistance potentially could improve therapeutic efficacy.