Resistance to Novel Antiandrogen Therapies in Metastatic Castration-Resistant Prostate Cancer

Resistance to Novel Antiandrogen Therapies in Metastatic Castration-Resistant Prostate Cancer

Despite the introduction of novel therapies that maximally decrease androgen-receptor (AR) signaling activity, metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease. Even though abiraterone and enzalutamide represent breakthroughs in the treatment of mCRPC and have demonst...

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Main Authors: Boudadi, Karim, Antonarakis, Emmanuel S.
Format: Online
Language:English
Published: Libertas Academica 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4798019/
id pubmed-4798019
recordtype oai_dc
spelling pubmed-47980192016-03-24 Resistance to Novel Antiandrogen Therapies in Metastatic Castration-Resistant Prostate Cancer Boudadi, Karim Antonarakis, Emmanuel S. Review Despite the introduction of novel therapies that maximally decrease androgen-receptor (AR) signaling activity, metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease. Even though abiraterone and enzalutamide represent breakthroughs in the treatment of mCRPC and have demonstrated significant survival benefits, a significant proportion of patients have primary resistance to these agents and virtually all patients develop secondary resistance. While the mechanisms of resistance to these agents are not fully understood, many hypotheses of AR-dependent and AR-independent mechanisms are emerging, including upregulation of AR and cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17), induction of AR splice variants, AR point mutations, upregulation of glucocorticoid receptor, activation of alternative oncogenic signaling pathways, neuroendocrine transformation, and immune evasion via programmed death-ligand 1 upregulation. The aim of this review is to summarize the most clinically relevant mechanisms of resistance to novel androgen-directed agents, focusing on escape from enzalutamide and abiraterone. Libertas Academica 2016-03-16 /pmc/articles/PMC4798019/ /pubmed/27013902 http://dx.doi.org/10.4137/CMO.S34534 Text en © 2016 the author(s), publisher and licensee Libertas Academica Ltd. This is an open-access article distributed under the terms of the Creative Commons CC-BY-NC 3.0 License.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Boudadi, Karim
Antonarakis, Emmanuel S.
spellingShingle Boudadi, Karim
Antonarakis, Emmanuel S.
Resistance to Novel Antiandrogen Therapies in Metastatic Castration-Resistant Prostate Cancer
author_facet Boudadi, Karim
Antonarakis, Emmanuel S.
author_sort Boudadi, Karim
title Resistance to Novel Antiandrogen Therapies in Metastatic Castration-Resistant Prostate Cancer
title_short Resistance to Novel Antiandrogen Therapies in Metastatic Castration-Resistant Prostate Cancer
title_full Resistance to Novel Antiandrogen Therapies in Metastatic Castration-Resistant Prostate Cancer
title_fullStr Resistance to Novel Antiandrogen Therapies in Metastatic Castration-Resistant Prostate Cancer
title_full_unstemmed Resistance to Novel Antiandrogen Therapies in Metastatic Castration-Resistant Prostate Cancer
title_sort resistance to novel antiandrogen therapies in metastatic castration-resistant prostate cancer
description Despite the introduction of novel therapies that maximally decrease androgen-receptor (AR) signaling activity, metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease. Even though abiraterone and enzalutamide represent breakthroughs in the treatment of mCRPC and have demonstrated significant survival benefits, a significant proportion of patients have primary resistance to these agents and virtually all patients develop secondary resistance. While the mechanisms of resistance to these agents are not fully understood, many hypotheses of AR-dependent and AR-independent mechanisms are emerging, including upregulation of AR and cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17), induction of AR splice variants, AR point mutations, upregulation of glucocorticoid receptor, activation of alternative oncogenic signaling pathways, neuroendocrine transformation, and immune evasion via programmed death-ligand 1 upregulation. The aim of this review is to summarize the most clinically relevant mechanisms of resistance to novel androgen-directed agents, focusing on escape from enzalutamide and abiraterone.
publisher Libertas Academica
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4798019/
_version_ 1613554222791393280

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