Role of Androgen Receptor Variants in Prostate Cancer: Report from the 2017 Mission Androgen Receptor Variants Meeting

Eur Urol. 2018 May;73(5):715-723. doi: 10.1016/j.eururo.2017.11.038. Epub 2017 Dec 16.

Abstract

Context: Although a number of studies have demonstrated the importance of constitutively active androgen receptor variants (AR-Vs) in prostate cancer, questions still remain about the precise role of AR-Vs in the progression of castration-resistant prostate cancer (CRPC).

Objective: Key stakeholders and opinion leaders in prostate cancer convened on May 11, 2017 in Boston to establish the current state of the field of AR-Vs.

Evidence acquisition: The meeting "Mission Androgen Receptor Variants" was the second of its kind sponsored by the Prostate Cancer Foundation (PCF). This invitation-only event was attended by international leaders in the field and representatives from sponsoring organizations (PCF and industry sponsors). Eighteen faculty members gave short presentations, which were followed by in-depth discussions. Discussions focused on three thematic topics: (1) potential of AR-Vs as biomarkers of therapeutic resistance; (2) role of AR-Vs as functionally active CRPC progression drivers; and (3) utility of AR-Vs as therapeutic targets in CRPC.

Evidence synthesis: The three meeting organizers synthesized this meeting report, which is intended to summarize major data discussed at the meeting and identify key questions as well as strategies for addressing these questions. There was a critical consensus that further study of the AR-Vs is an important research focus in CRPC. Contrasting views and emphasis, each supported by data, were presented at the meeting, discussed among the participants, and synthesized in this report.

Conclusions: This article highlights the state of knowledge and outlines the most pressing questions that need to be addressed to advance the AR-V field.

Patient summary: Although further investigation is needed to delineate the role of androgen receptor (AR) variants in metastatic castration-resistant prostate cancer, advances in measurement science have enabled development of blood-based tests for treatment selection. Detection of AR variants (eg, AR-V7) identified a patient population with poor outcomes to existing AR-targeting therapies, highlighting the need for novel therapeutic agents currently under development.

Keywords: Abiraterone; Androgen receptor variant 7; Androgen receptor variants; Castration-resistant prostate cancer; Enzalutamide.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aged
  • Androgen Antagonists / therapeutic use*
  • Androstenes / therapeutic use
  • Biomarkers, Tumor / blood
  • Congresses as Topic
  • Disease-Free Survival
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Phenylthiohydantoin / analogs & derivatives*
  • Phenylthiohydantoin / therapeutic use
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / metabolism*
  • Prostatic Neoplasms, Castration-Resistant / mortality
  • Receptors, Androgen / blood*
  • Risk Assessment
  • Survival Analysis
  • Treatment Outcome

Substances

  • Androgen Antagonists
  • Androstenes
  • Biomarkers, Tumor
  • MDV 3100
  • Receptors, Androgen
  • Phenylthiohydantoin
  • abiraterone