A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer

Katie Joanna Miller; Isla Henry; Zoe Maylin; Christopher Smith; Einthavy Arunachalam; Hardev Pandha; Mohammad Asim

doi:10.3389/fonc.2023.1129140

A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer

Front Oncol. 2023 Mar 1:13:1129140. doi: 10.3389/fonc.2023.1129140. eCollection 2023.

Authors

Katie Joanna Miller¹, Isla Henry¹, Zoe Maylin¹, Christopher Smith¹, Einthavy Arunachalam¹, Hardev Pandha¹, Mohammad Asim¹

Affiliation

¹ Department of Clinical & Experimental Medicine, University of Surrey, Guildford, United Kingdom.

Abstract

Persistent androgen receptor (AR) signalling is the main driver of prostate cancer (PCa). Truncated isoforms of the AR called androgen receptor variants (AR-Vs) lacking the ligand binding domain often emerge during treatment resistance against AR pathway inhibitors such as Enzalutamide. This review discusses how AR-Vs drive a more aggressive form of PCa through the regulation of some of their target genes involved in oncogenic pathways, enabling disease progression. There is a pressing need for the development of a new generation of AR inhibitors which can repress the activity of both the full-length AR and AR-Vs, for which the knowledge of differentially expressed target genes will allow evaluation of inhibition efficacy. This review provides a detailed account of the most common variant, AR-V7, the AR-V7 regulated genes which have been experimentally validated, endeavours to understand their relevance in aggressive AR-V driven PCa and discusses the utility of the downstream protein products as potential drug targets for PCa treatment.

Keywords: AR-V7; cancer; castration; gene; prostate.

Publication types

Review

Grants and funding

This work was supported by a doctoral college of the University of Surrey through their PhD studentship award (ZM), the Medical Research Council (UK), the Prostate Cancer Foundation (USA) and the Prostate Project (MA), by studentship/postdoctoral placement supported by HOX therapeutics ltd. funding (EA, IH) and by Univar studentship funding (CS). The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.