Targeting Androgen Receptor Variants in Castration-Resistant Prostate Cancer (CRPC): A Comprehensive Review

Mercy Latricia

Faculty of Pharmacy Kampala International University Uganda

Email: latricia.mercy@studwc.kiu.ac.ug

ABSTRACT

Castration-resistant prostate cancer (CRPC) represents a significant clinical challenge due to its aggressive progression despite androgen deprivation therapy (ADT). One of the key mechanisms driving CRPC is the emergence of androgen receptor (AR) variants (AR-Vs), particularly AR-V7, which remain active in low-androgen environments and promote tumor survival and proliferation. These AR-Vs lack the ligand-binding domain but retain the transcriptionally active N-terminal domain, making them resistant to conventional AR-targeted therapies. This review comprehensively explores the biology of AR-Vs, their role in CRPC progression, and recent advancements in targeting these variants. Emerging therapeutic strategies include AR N-terminal domain inhibitors, spliceosome-targeting therapies, and novel degraders that specifically address AR-Vs. The review also discusses potential biomarkers for AR-V-driven CRPC and highlights the challenges in translating preclinical findings into effective clinical interventions. Targeting AR-Vs offers a promising avenue for overcoming resistance in CRPC, providing new hope for patients with advanced disease.

Keywords: Castration-resistant prostate cancer, androgen receptor variants, AR-V7, androgen deprivation therapy, N-terminal domain inhibitors, spliceosome-targeting therapies

CITE AS: Mercy Latricia. (2024). Targeting Androgen Receptor Variants in Castration-Resistant Prostate Cancer (CRPC): A Comprehensive Review. Research Output Journal of Public Health and Medicine 4(2):33-37. https://doi.org/10.59298/ROJPHM/2024/423337