Abstract

Understanding and targeting the mechanisms of resistance to enzalutamide in castration resistant prostate cancer.

Background: Enzalutamide (MDV3100, XTANDI) is a second generation androgen receptor inhibitor that is designed for the treatment of castration-resistant prostate cancer (CRPC) and has prolonged survival time. The mechanisms of mdv3100 resistance have not yet been clearly clarified and the majority of treated patients, innate or acquiring resistance invariably arises.

Objective: The purpose of this review is to summarize the main data available on the mechanisms of resistance to mdv3100. Understanding how the resistance aroused may have clinical implications in underlying the usefulness of prognostic and predictive biomarkers in daily practice and improving the strategies.

Results: Resistance to MDV3100 could be basically divided into two distinct pathways, either dependent or independent of the androgen receptor activity. Androgen receptor (AR) axis is sitll the most important pathway for prostate cancer cells and it is still currently regarded as a critical resistant mechanism.

Conclusion: Targeting these newly identified signals, especially AR axis, could be potentially overcome through novel therapeutic agents, synergically improve the ADT in CRPC.

Keywords: Castration-resistant prostate cancer, enzalutamide, drug resistance, androgen receptor, biomarker, inhibitor.

Graphical Abstract