Regulation of androgen receptor variants in prostate cancer

doi:10.1016/j.ajur.2020.01.001

Asian Journal of Urology, 2020, 7 (3): 251-257 doi: 10.1016/j.ajur.2020.01.001

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Regulation of androgen receptor variants in prostate cancer

Yezi Zhu^a,b,Jun Luo^a,*(

)

^a Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA
^b LIVESTRONG Cancer Institutes, The University of Texas, Austin, TX, USA

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Abstract

Aberrant activation of androgen receptor (AR) signaling occurs in patients treated with AR-targeted therapies, contributing to the development of castration-resistant prostate cancer (CRPC) and therapeutic resistance. Over the past decade, many AR variants (AR-Vs) have been identified in prostate cancer cell lines and clinical CRPC specimens. These AR-Vs lack the COOH-terminal ligand-binding domain (LBD), and may mediate constitutively active AR signaling acquired following AR-targeting therapies. AR splice variant-7 (AR-V7), one of the most well characterized AR-Vs, can be reliably measured in tissue and liquid biopsy specimens, and blood-based detection of AR-V7 is a reliable indicator of poor outcome to relatively novel hormonal therapies (NHT) such as abiraterone and enzalutamide in men with metastatic CRPC (mCRPC). Given the important clinical implication of AR-Vs, this short review will focus on studies addressing how AR-Vs are regulated in prostate cancer. With regard to the molecular origin of AR-Vs, it is established that expression of AR-Vs is highly correlated with androgen deprivation and suppression of AR signaling. Therapeutic targeting of the AR axis may result in active transcription of the AR gene, elevated activities of certain components of the mRNA splicing machinery, as well as AR genomic alterations, all of which may explain the molecular origin of AR-Vs. Although a unified hypothesis is currently lacking, existing data suggest that elevated expression of AR-Vs, which in general occurs quite specifically in a cellular environment where the canonical AR signaling is suppressed, is driven by both genomic and epigenomic features acquired in the development of CRPC.

Key words： Androgen receptor Androgen receptor splice variant-7 Castration-resistant prostate cancer

Received: 06 September 2019 Available online: 20 July 2020

Corresponding Authors: Jun Luo E-mail: jluo1@jhmi.edu

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Yezi Zhu,Jun Luo. Regulation of androgen receptor variants in prostate cancer[J]. Asian Journal of Urology, 2020, 7(3): 251-257.

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http://www.ajurology.com/EN/10.1016/j.ajur.2020.01.001 OR http://www.ajurology.com/EN/Y2020/V7/I3/251

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