Lessons from tissue compartment-specific analysis of androgen receptor alterations in prostate cancer

Mark Daniel, Scott M. Dehm

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations

Abstract

Androgen receptor (AR) splice variants (AR-Vs) are constitutively active transcription factors that function in the absence of ligand. AR-Vs represent one of several AR re-activation mechanisms utilized by prostate cancer to circumvent first-line androgen deprivation therapy. Second line therapies such as enzalutamide and abiraterone are treatments that re-target components of the androgen/AR axis. However, these second line therapies do not benefit all patients, and patients that do receive initial benefit can develop resistance rapidly. Alterations in components of the androgen/AR axis, including expression of AR-Vs, appear to be linked to primary as well as secondary resistance to second line therapies. However, some key conclusions appear to differ depending on the tissue compartment and measurement platform utilized for analysis. In this review, alterations in AR and the broader AR pathway will be examined in the context of primary prostate cancer tissue, metastatic castration-resistant prostate cancer tissue, circulating tumor cells, and circulating cell-free tumor DNA. Questions regarding the utility of AR-V measurements to provide prognostic information or predict patient responses to AR-targeted therapies will be addressed.

Original languageEnglish (US)
Pages (from-to)28-37
Number of pages10
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume166
DOIs
StatePublished - Feb 1 2017

Bibliographical note

Funding Information:
SMD is currently funded by a Movember/Prostate Cancer Foundation Challenge Award, American Cancer Society Research Scholar Grant RSG-12-031-01-TBE, NIH grant R01CA174777, US Department of Defense Prostate Cancer Research Program grants W81XWH-12-2-0093, W81XWH-13-1-0518, W81XWH-15-1-0633, and W81XWH-15-1-0501, and a grant from the Minnesota Partnership for Biotechnology and Medical Genomics.

Keywords

  • Androgen receptor splice variant
  • Castration-resistant prostate cancer
  • Circulating tumor cell
  • Prostate cancer

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