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Updated: Apr 2, 2026

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
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Androgen receptor splice variant 7 expression levels distinguish AR-mutated from nonmutated metastatic

Alec Paschalis1,2, Ines Figueiredo1, Denisa Bogdan1

  • 1The Institute of Cancer Research, London, United Kingdom.

The Journal of Clinical Investigation
|April 1, 2026
PubMed

Insights

Androgen receptor (AR) mutations in metastatic castration-resistant prostate cancer (mCRPC) are linked to lower AR splice variant 7 (AR-V7) expression. This finding suggests AR mutation status may predict patient response to AR pathway inhibitors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Metastatic castration-resistant prostate cancer (mCRPC) is a significant clinical challenge.
  • New androgen receptor pathway inhibitors (ARPIs) show promise, particularly in AR-mutated mCRPC.
  • The role of AR splice variants, such as AR-V7, in treatment resistance is under investigation.

Purpose of the Study:

  • To investigate the relationship between AR mutations and AR-V7 expression in mCRPC.
  • To determine if AR-V7 levels correlate with sensitivity to ARPIs in AR-mutated mCRPC.
  • To explore the potential of AR mutation status as a predictive biomarker for AR-directed therapies.

Main Methods:

  • Analysis of mCRPC tissue biopsies for AR mutation status and AR-V7 protein expression.
  • Correlation of AR mutation and AR-V7 levels with overall survival and response to ARPIs.
  • Investigation of potential mechanisms, including splicing factor expression, underlying observed differences.

Main Results:

  • mCRPC tissue biopsies with detectable AR mutations exhibited significantly lower AR-V7 protein expression.
  • Lower AR-V7 expression in AR-mutated mCRPC was associated with better overall survival.
  • AR-mutated mCRPC demonstrated enhanced sensitivity to ARPIs, independent of global splicing events.

Conclusions:

  • AR-mutated mCRPC frequently presents with low AR-V7 expression.
  • Low AR-V7 expression in AR-mutated mCRPC likely contributes to enhanced sensitivity to ARPIs.
  • AR mutation status may serve as a valuable biomarker for predicting response to AR-directed therapies in mCRPC.
Keywords:
Clinical ResearchOncologyProstate cancer

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