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

Overview

Journal Clin Med Insights Oncol

Publisher Sage Publications

Specialty Oncology

Date 2016 Mar 26

PMID 27013902

Citations 57

Authors

Karim Boudadi

Emmanuel S Antonarakis

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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