Enzalutamide: Development from bench to bedside.

Urologic Oncology
R M Bambury, Howard I Scher

Abstract

Prostate tissue, whether benign or malignant, is heavily dependent on androgen receptor (AR) signaling for growth and proliferation. Androgen deprivation therapy has been standard of care for management of metastatic prostate cancer for the past 70 years. AR antagonists were developed to further abrogate signaling through this pathway by competitive inhibition of the receptor. First-generation compounds such as bicalutamide had modest efficacy, and in the setting of AR overexpression or specific mutations in the AR ligand-binding domain, these early compounds had partial agonist properties that could stimulate tumor growth. Enzalutamide was developed to overcome these deficiencies, and here, we present the story of its preclinical discovery, clinical development, and ultimate approval as a standard-of-care therapy for castration-resistant prostate cancer. Also discussed are ongoing efforts to elucidate mechanisms of resistance to this agent as well as studies that are investigating its role in other prostate cancer disease states and other cancer types.

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Citations

Sep 20, 2015·Annals of the New York Academy of Sciences·Suman BhattacharyaSteve van Os
Mar 30, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mark N Stein, Thomas L Jang
Nov 2, 2018·Endocrine-related Cancer·Simon LinderStefan Prekovic
Nov 1, 2018·Biomedit︠s︡inskai︠a︡ khimii︠a︡·J E VorontsovaO B Simonova
Sep 11, 2019·Nucleic Acids Research·Fuwen YuanQianben Wang
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Jun 9, 2017·Molecular Cancer Research : MCR·Rahul AggarwalMichael J Evans
Oct 2, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yongjun QuanXiaodong Zhang

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