Advances in the Current Understanding of the Mechanisms Governing the Acquisition of Castration-Resistant Prostate Cancer

SIMPLE SUMMARY: Castration-resistant prostate cancer (CRPC) is an advanced form of prostate cancer with a low survival rate, as the CRPC patients only survive for 9–13 months on average. In this narrative review, we first outline the most common androgen receptor (AR) receptor-related mechanisms, highlighting the important role of ARs in the development of CRPC. We also discuss the key importance of non-coding RNAs (ncRNAs) in this setting, including long ncRNAs and microRNAs. Overall, studies of the molecular biological mechanisms governing the CRPC will facilitate the development of appropriate targeted therapeutics, improving treatment options for the CRPC patients. ABSTRACT: Despite aggressive treatment and androgen-deprivation therapy, most prostate cancer patients ultimately develop castration-resistant prostate cancer (CRPC), which is associated with high mortality rates. However, the mechanisms governing the development of CRPC are poorly understood, and androgen receptor (AR) signaling has been shown to be important in CRPC through AR gene mutations, gene overexpression, co-regulatory factors, AR shear variants, and androgen resynthesis. A growing number of non-AR pathways have also been shown to influence the CRPC progression, including the Wnt and Hh pathways. Moreover, non-coding RNAs have been identified as important regulators of the CRPC pathogenesis. The present review provides an overview of the relevant literature pertaining to the mechanisms governing the molecular acquisition of castration resistance in prostate cancer, providing a foundation for future, targeted therapeutic efforts.