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Updated: Aug 14, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

Drug Resistance of Enzalutamide in CRPC

Xuedong Chen1, Jieyang Lu1, Liqun Xia1

  • 1Department of Urology, Sir Run-Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China.

Current Drug Targets
|April 18, 2017
PubMed

Insights

Mechanisms of resistance to enzalutamide (XTANDI) in castration-resistant prostate cancer (CRPC) are not fully understood. Targeting androgen receptor (AR) signaling pathways may overcome resistance and improve treatment strategies.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Enzalutamide (XTANDI) is a second-generation androgen receptor inhibitor used for castration-resistant prostate cancer (CRPC).
  • Resistance to enzalutamide, either innate or acquired, develops in most treated patients, necessitating a deeper understanding of its mechanisms.
  • The precise mechanisms underlying enzalutamide resistance remain incompletely clarified.

Purpose of the Study:

  • To review and summarize current data on the mechanisms of resistance to enzalutamide (MDV3100).
  • To explore the clinical implications of understanding resistance mechanisms for prognostic and predictive biomarkers.
  • To inform improved therapeutic strategies for CRPC patients.

Main Methods:

  • Literature review of studies investigating enzalutamide resistance in CRPC.
  • Analysis of identified resistance pathways, focusing on androgen receptor (AR) activity.
  • Synthesis of findings to identify potential therapeutic targets.

Main Results:

  • Resistance to enzalutamide can occur through pathways dependent or independent of androgen receptor (AR) activity.
  • The AR signaling axis remains a critical factor in prostate cancer cell survival and a key mechanism of resistance.
  • Distinct molecular alterations contribute to both AR-dependent and AR-independent resistance phenotypes.

Conclusions:

  • Understanding enzalutamide resistance mechanisms is crucial for clinical practice and treatment optimization.
  • Targeting AR signaling pathways and other identified resistance mechanisms holds promise for overcoming resistance.
  • Novel therapeutic agents, used synergistically with androgen deprivation therapy (ADT), could improve outcomes for CRPC patients.
Keywords:
Castration-resistant prostate cancerandrogen receptorbiomarkerdrug resistanceenzalutamideinhibitor.

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