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Molecular pathways: targeting resistance in the androgen receptor for therapeutic benefit

Elahe A Mostaghel1, Stephen R Plymate, Bruce Montgomery

  • 1Authors' Affiliations: Division of Clinical Research, Fred Hutchinson Cancer Research Center; and Department of Medicine, University of Washington, Seattle, Washington.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|December 6, 2013
PubMed

Insights

Androgen receptor (AR) signaling drives prostate cancer. Understanding AR resistance mechanisms and developing novel therapies offers hope for improved cancer control.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Androgen receptor (AR) signaling is a key driver in prostate cancer development and progression.
  • Therapeutic interventions targeting AR signaling are crucial for managing prostate cancer.

Purpose of the Study:

  • To elucidate potential points of therapeutic intervention in AR signaling.
  • To identify and understand mechanisms of resistance to AR suppression therapies.

Main Methods:

  • Review of current literature on AR signaling in prostate cancer.
  • Analysis of known and emerging resistance mechanisms.
  • Evaluation of novel therapeutic agents and cotargeting strategies.

Main Results:

  • Identified several mechanisms of resistance, including alternative androgen sources, AR expression/mutation, AR variants, cofactor recruitment alterations, and AR-driven gene fusions.
  • Highlighted the increasing relevance of these mechanisms under effective AR suppression.
  • Showcased new therapeutic agents (e.g., enzalutamide, EPI-001, HSP90/PARP inhibitors) and cotargeting approaches.

Conclusions:

  • A comprehensive understanding of AR signaling and resistance is vital for effective prostate cancer treatment.
  • Novel therapeutic strategies show promise for achieving more complete and durable control of AR-mediated prostate cancer growth.

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