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The potential of AR-V7 as a therapeutic target

Takuma Uo1, Stephen R Plymate1,2, Cynthia C Sprenger1

  • 1a Department of Medicine , University of Washington , Seattle , WA , USA.

Expert Opinion on Therapeutic Targets
|February 9, 2018
PubMed
Abstract

Insights

The androgen receptor variant AR-V7 (androgen receptor variant 7) is a key factor in castration-resistant prostate cancer (CRPC) treatment resistance. New therapies targeting AR-V7 signaling are crucial for improving patient outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The androgen receptor variant AR-V7 (androgen receptor variant 7) is implicated in treatment resistance in castration-resistant prostate cancer (CRPC).
  • Understanding AR-V7's role is critical for developing effective therapies against advanced prostate cancer.

Purpose of the Study:

  • To review mechanisms of AR-V7 generation and its role in anti-androgen receptor (AR) therapy resistance.
  • To discuss current and emerging therapeutic strategies targeting AR-V7 signaling in CRPC.
  • To evaluate the status of preclinical and clinical studies investigating AR-V7-targeted agents.

Main Methods:

  • Literature review of proposed mechanisms of drug resistance related to AR-V7 status.
  • Analysis of AR-V7 generation, transcriptome, cistrome, and interactome.
  • Survey of pharmacological agents targeting AR-V7 and pan-AR signaling.
  • Assessment of preclinical and clinical studies on AR-V7-targeted therapies.

Main Results:

  • AR-V7 is a significant mechanism of resistance to current anti-AR therapies in CRPC.
  • Multiple strategies are under development to target AR-V7 and pan-AR signaling.
  • The precise role of AR-V7 as a driver versus a bystander in CRPC progression requires further elucidation.

Conclusions:

  • AR-V7 represents a validated therapeutic target in CRPC.
  • Combination therapies involving selective AR-V7 blockade and pan-AR inhibition show promise.
  • Future strategies may involve combining anti-AR therapies with agents that prevent the activation and enrichment of AR-negative tumor cells.
Keywords:
AR-V7Adaptive resistanceandrogen receptorbiomarkercastration-resistant prostate cancer

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