Targeting Androgen Receptor Variants in Castration-Resistant Prostate Cancer (CRPC)

Abstract

Castration-resistant prostate cancer (CRPC) remains a lethal stage of prostate cancer, characterized by resistance to androgen deprivation therapy (ADT) and poor clinical prognosis. One of the key drivers in CRPC progression is the androgen receptor (AR), specifically the emergence of androgen receptor variants (AR-Vs) that sustain AR signaling even in the absence of androgens. AR-Vs, such as AR-V7, promote androgen-independent activation of oncogenic pathways, leading to uncontrolled cell proliferation and therapeutic resistance. Targeting AR-Vs offers a promising therapeutic strategy to manage CRPC effectively. This review explores the molecular mechanisms underpinning AR-V expression, examines the roles of major AR variants in CRPC progression, and evaluates current and emerging therapies targeting AR-Vs. By summarizing recent advancements and the limitations of current approaches, we highlight potential future directions to improve therapeutic outcomes for CRPC patients. Keywords: Androgen receptor variants, Castration-resistant prostate cancer, AR-V7, Androgen deprivation therapy, Targeted therapy, Oncogenic pathways