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Updated: Feb 8, 2026

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
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Mechanisms and Approaches for Overcoming Enzalutamide Resistance in Prostate Cancer

Alexandra Vander Ark1, Jingchen Cao1, Xiaohong Li1

  • 1Program for Skeletal Disease and Tumor Microenvironment, Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, MI, United States.

Frontiers in Oncology
|June 19, 2018
PubMed

Insights

Enzalutamide resistance in prostate cancer is a major challenge. This review explores resistance mechanisms like AR mutations and tumor microenvironment factors, and discusses strategies to overcome them.

Area of Science:

  • Oncology
  • Molecular Biology
  • Urology

Background:

  • Enzalutamide is a key treatment for castration-resistant prostate cancer (CRPC) with bone metastases.
  • It inhibits androgen receptor (AR) signaling, crucial for prostate cancer growth.
  • Acquired resistance limits enzalutamide's long-term efficacy in CRPC patients.

Purpose of the Study:

  • To review the major mechanisms of acquired enzalutamide resistance in prostate cancer.
  • To discuss current and emerging strategies for overcoming this resistance.
  • To identify future research directions and challenges in enzalutamide resistance.

Main Methods:

  • Literature review of studies on enzalutamide resistance in prostate cancer.
  • Analysis of genetic mutations, splice variants, and signaling pathways contributing to resistance.
  • Evaluation of the role of intratumoral androgen biosynthesis and the tumor microenvironment.

Main Results:

  • Key resistance mechanisms include AR alterations (mutations, splice variants), bypass signaling pathways, intratumoral androgen production, lineage plasticity, and tumor microenvironment influences.
  • Various strategies are being explored to overcome resistance, addressing each identified mechanism.
  • Significant challenges and limitations exist in current therapeutic approaches.

Conclusions:

  • Understanding diverse resistance mechanisms is critical for improving CRPC treatment outcomes.
  • Developing combination therapies targeting multiple resistance pathways offers promising therapeutic opportunities.
  • Further research is needed to address emerging questions and optimize strategies against enzalutamide resistance.
Keywords:
androgen receptor mutantsandrogen receptor splice variantsbypasscastration-resistant prostate cancerenzalutamide resistanceintratumoral androgen biosynthesislineage plasticitytumor microenvironment

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