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Galeterone for the treatment of advanced prostate cancer: the evidence to date

Authors Bastos D, Antonarakis E

Received 17 May 2016

Accepted for publication 22 June 2016

Published 15 July 2016 Volume 2016:10 Pages 2289—2297

DOI https://doi.org/10.2147/DDDT.S93941

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 3

Editor who approved publication: Dr James Janetka


Diogo A Bastos,1 Emmanuel S Antonarakis2

1Department of Oncology, Hospital Sirio-Libanes, Sao Paulo, Brazil; 2Department of Oncology and Urology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Abstract: Major advances have been achieved recently in the treatment of metastatic castration-resistant prostate cancer, resulting in significant improvements in quality of life and survival with the use of several new agents, including the next-generation androgen receptor (AR)-targeted drugs abiraterone and enzalutamide. However, virtually all patients will eventually progress on these therapies and most will ultimately die of treatment-refractory metastatic disease. Recently, several mechanisms of resistance to AR-directed therapies have been uncovered, including the AR splice variant 7 (AR-V7), which is a ligand-independent constitutionally-active form of the AR that has been associated with poor outcomes to abiraterone and enzalutamide. Galeterone, a potent anti-androgen with three modes of action (CYP17 lyase inhibition, AR antagonism, and AR degradation), is a novel agent under clinical development that could potentially target both full-length AR and aberrant AR, including AR-V7. In this manuscript, we will first discuss the biological mechanisms of action of galeterone and then review the safety and efficacy data from Phase I and II clinical studies of galeterone in patients with metastatic castration-resistant prostate cancer. A Phase III study of galeterone (compared against enzalutamide) in AR-V7-positive patients is currently underway, and represents the first pivotal trial using a biomarker-selection design in this disease.

Keywords: galeterone, AR splice variants, AR-V7, castration-resistant prostate cancer

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