Enzalutamide and blocking androgen receptor in advanced prostate cancer: lessons learnt from the history of drug development of antiandrogens

Research and Reports in Urology
Yusuke Ito, Marianne D Sadar

Abstract

Enzalutamide is a nonsteroidal antiandrogen for the treatment of metastatic castration-resistant prostate cancer (mCRPC) both before and after chemotherapy. Enzalutamide is more effective than its predecessor bicalutamide, which was analyzed in head-to-head studies of patients with CRPC. This family of nonsteroidal antiandrogens is now comprised of four drugs approved by the US Food and Drug Administration with two investigational drugs in clinical trials. Antiandrogens have been employed clinically for more than five decades to provide a rich resource of information. Steady-state concentration minimums (Cmin or trough) in the range of ~1-13 μg/mL are measured in patients at therapeutic doses. Interestingly, enzalutamide which is considered to have strong affinity for the androgen receptor (AR) requires Cmin levels >10 μg/mL. The sequence of antiandrogens and the clinical order of application in regard to other drugs that target the androgen axis remain of high interest. One novel first-in-class drug, called ralaniten, which binds to a unique region in the N-terminus domain of both the full-length and the truncated constitutively active splice variants of the AR, is currently in clinical trials for patients who previously recei...Continue Reading

Citations

Sep 21, 2018·Journal of Biomolecular Structure & Dynamics·George Nicolae Daniel IonGeorge Mihai Nitulescu
Jan 15, 2019·Endocrine Connections·Michael UlmRamesh Narayanan
May 17, 2019·Expert Opinion on Therapeutic Patents·Shinya Fujii, Hiroyuki Kagechika
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jana KvízováSilvie Rimpelová
May 8, 2020·Journal of the American Chemical Society·Jeroen B I SapVéronique Gouverneur

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Methods Mentioned

BETA
chemical
castration
nuclear translocation
xenografts

Clinical Trials Mentioned

NCT01946204
NCT02257736
NCT02200614
NCT02799602
NCT02606123

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