Lookup NU author(s): Dr Urszula McClurg,
Dr Mahsa Azizyan,
Dr Sirintra Nakjang,
Professor Craig Robson
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Metastatic castration resistant prostate cancer is one of the main causes of male cancer associated deaths worldwide. Development of resistance is inevitable in patients treated with anti-androgen therapies. This highlights a need for novel therapeutic strategies that would be aimed upstream of the androgen receptor (AR). Here we report that the novel small molecule anti-androgen, galeterone targets USP12 and USP46, two highly homologous deubiquitinating enzymes that control the AR-AKT-MDM2-P53 signalling pathway. Consequently, galeterone is effective in multiple models of prostate cancer including both castrate resistant and AR-negative prostate cancer. However, we have observed that USP12 and USP46 selectively regulate full length AR protein but not the AR variants. This is the first report of deubiquitinating enzyme targeting as a strategy in prostate cancer treatment which we show to be effective in multiple, currently incurable models of this disease.
Author(s): McClurg UL, Azizyan M, Dransfield DT, Namdev N, Chit NCTH, Nakjang S, Robson CN
Publication type: Article
Publication status: Published
Print publication date: 18/05/2018
Online publication date: 18/05/2018
Acceptance date: 10/02/2018
Date deposited: 21/05/2018
ISSN (electronic): 1949-2553
Publisher: Impact Journals LLC
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