Androgen receptor rediscovered: The new biology and targeting the androgen receptor therapeutically

Charles J. Ryan, Donald J. Tindall

Research output: Contribution to journalReview article

178 Scopus citations

Abstract

Discoveries over the past decade suggest that castration-resistant prostate cancer (CRPC) is sensitive, but not resistant to, further manipulation of the androgen-androgen receptor (AR) axis. Several new therapies that target this axis have demonstrated clinical activity. In this article, preclinical and clinical findings occurring in the field of AR-targeted therapies are reviewed. Reviews of scientific and clinical development are divided into those occurring prereceptor (androgen production and conversion) and at the level of the receptor (AR aberrations and therapies targeting AR directly). Intracrine androgen production and AR amplification, among others, are among the principal aberrancies driving CRPC growth. Phase III data with abiraterone acetate and phase II data with MDV-3100, along with other similar therapies, confirm for the clinician that the scientific findings related to persistent AR signaling in a castrate milieu can be harnessed to produce significant clinical benefit for patients with the disease. Studies aimed at optimizing the timing of their use and exploring the mechanisms of resistance to these therapies are under way. The clinical success of therapies that directly target androgen synthesis as well as the most common aberrancies of the AR confirm that prostate cancer retains dependence on AR signaling, even in the castrate state.

Original languageEnglish (US)
Pages (from-to)3651-3658
Number of pages8
JournalJournal of Clinical Oncology
Volume29
Issue number27
DOIs
StatePublished - Sep 20 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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