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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 in castration-resistant prostate cancer: Clinical considerations

Alan H Bryce1, Emmanuel S Antonarakis2

  • 1Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, Arizona, USA.

International Journal of Urology : Official Journal of the Japanese Urological Association
|June 4, 2016
PubMed

Insights

Androgen receptor splice variant 7 (AR-V7) is a key driver of resistance in prostate cancer treatments. Detecting AR-V7 may guide the selection of effective therapies like taxane chemotherapy for metastatic castration-resistant prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Prostate cancer cells develop resistance to androgen deprivation therapy (ADT) and novel androgen receptor (AR)-directed treatments through constitutively-active AR splice variants.
  • Androgen receptor splice variant 7 (AR-V7) is the most prevalent variant in clinical samples.
  • Emerging evidence links AR-V7 to primary and acquired resistance against next-generation AR pathway inhibitors, including abiraterone and enzalutamide.

Purpose of the Study:

  • To review preclinical data on AR-V7 structure and function.
  • To summarize current clinical data on AR-V7 as a biomarker in metastatic castration-resistant prostate cancer (mCRPC).
  • To highlight therapeutic strategies targeting AR-V7-expressing prostate cancer.

Main Methods:

  • Literature review of preclinical studies on AR-V7.
  • Analysis of existing clinical data for AR-V7 in mCRPC.
  • Identification of therapeutic approaches for AR-V7-positive tumors.

Main Results:

  • AR-V7 is a common adaptive response enabling prostate cancer cells to evade ADT and AR-directed therapies.
  • Tumoral AR-V7 presence correlates with resistance to abiraterone and enzalutamide.
  • Taxane chemotherapy may maintain efficacy irrespective of AR-V7 status, suggesting its utility as a predictive biomarker.

Conclusions:

  • AR-V7 is a significant biomarker for predicting treatment response in mCRPC.
  • AR-V7 status can guide the selection of therapies, potentially favoring taxanes over AR pathway inhibitors in resistant cases.
  • Targeting AR-V7-expressing prostate cancer is a promising therapeutic avenue.
Keywords:
androgenandrogen receptor splice variant 7hormone therapyprostate cancerresistance

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