The Crucial Role of AR-V7 in Enzalutamide-Resistance of Castration-Resistant Prostate Cancer

Simple Summary Androgen receptor splice variant 7 (AR-V7) has always been considered a key driver for triggering enzalutamide resistance of castration-resistant prostate cancer (CRPC). In recent years, both the homeostasis of AR-V7 protein and AR-V7's relationship with LncRNAs have gained great attention with in-depth studies. Starting from protein stability and LncRNA, the paper discusses and summarizes the mechanisms and drugs that affect the CRPC patients' sensitivity to enzalutamide by regulating the protein or transcriptional stability of AR-V7, hoping to provide therapeutic ideas for subsequent research to break through the CRPC therapeutic bottleneck. Prostate cancer (PCa) has the second highest incidence of malignancies occurring in men worldwide. The first-line therapy of PCa is androgen deprivation therapy (ADT). Nonetheless, most patients progress to castration-resistant prostate cancer (CRPC) after being treated by ADT. As a second-generation androgen receptor (AR) antagonist, enzalutamide (ENZ) is the current mainstay of new endocrine therapies for CRPC in clinical use. However, almost all patients develop resistance during AR antagonist therapy due to various mechanisms. At present, ENZ resistance (ENZR) has become challenging in the clinical treatment of CRPC. AR splice variant 7 (AR-V7) refers to a ligand-independent and constitutively active variant of the AR and is considered a key driver of ENZR in CRPC. In this review, we summarize the mechanisms and biological behaviors of AR-V7 in ENZR of CRPC to contribute novel insights for CRPC therapy.