Developing New Treatment Options for Castration-Resistant Prostate Cancer and Recurrent Disease

Prostate cancer (PCa) is a major diagnosed cancer among men globally, and about 20% of patients develop metastatic prostate cancer (mPCa) in the initial diagnosis. PCa is a typical androgen-dependent disease; thus, hormonal therapy is commonly used as a standard care for mPCa by inhibiting androgen receptor (AR) activities, or androgen metabolism. Inevitably, almost all PCa will acquire resistance and become castration-resistant PCa (CRPC) that is associated with AR gene mutations or amplification, the presence of AR variants, loss of AR expression toward neuroendocrine phenotype, or other hormonal receptors. Treating CRPC poses a great challenge to clinicians. Research efforts in the last decade have come up with several new anti-androgen agents to prolong overall survival of CRPC patients. In addition, many potential targeting agents have been at the stage of being able to translate many preclinical discoveries into clinical practices. At this juncture, it is important to highlight the emerging strategies including small-molecule inhibitors to AR variants, DNA repair enzymes, cell survival pathway, neuroendocrine differentiation pathway, radiotherapy, CRPC-specific theranostics and immune therapy that are underway or have recently been completed.