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

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...

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Autores principales: Miller, Katie Joanna, Henry, Isla, Maylin, Zoe, Smith, Christopher, Arunachalam, Einthavy, Pandha, Hardev, Asim, Mohammad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10014620/
https://www.ncbi.nlm.nih.gov/pubmed/36937454
http://dx.doi.org/10.3389/fonc.2023.1129140
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author Miller, Katie Joanna
Henry, Isla
Maylin, Zoe
Smith, Christopher
Arunachalam, Einthavy
Pandha, Hardev
Asim, Mohammad
author_facet Miller, Katie Joanna
Henry, Isla
Maylin, Zoe
Smith, Christopher
Arunachalam, Einthavy
Pandha, Hardev
Asim, Mohammad
author_sort Miller, Katie Joanna
collection PubMed
description 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.
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spelling pubmed-100146202023-03-16 A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer Miller, Katie Joanna Henry, Isla Maylin, Zoe Smith, Christopher Arunachalam, Einthavy Pandha, Hardev Asim, Mohammad Front Oncol Oncology 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. Frontiers Media S.A. 2023-03-01 /pmc/articles/PMC10014620/ /pubmed/36937454 http://dx.doi.org/10.3389/fonc.2023.1129140 Text en Copyright © 2023 Miller, Henry, Maylin, Smith, Arunachalam, Pandha and Asim https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Miller, Katie Joanna
Henry, Isla
Maylin, Zoe
Smith, Christopher
Arunachalam, Einthavy
Pandha, Hardev
Asim, Mohammad
A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer
title A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer
title_full A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer
title_fullStr A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer
title_full_unstemmed A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer
title_short A compendium of Androgen Receptor Variant 7 target genes and their role in Castration Resistant Prostate Cancer
title_sort compendium of androgen receptor variant 7 target genes and their role in castration resistant prostate cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10014620/
https://www.ncbi.nlm.nih.gov/pubmed/36937454
http://dx.doi.org/10.3389/fonc.2023.1129140
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