Novel Insights into Molecular Indicators of Response and Resistance to Modern Androgen-Axis Therapies in Prostate Cancer

John L. Silberstein, Maritza N. Taylor, Emmanuel S. Antonarakis

Research output: Contribution to journalReview article

Abstract

While androgen ablation remains a mainstay for advanced prostate cancer therapy, nearly all patients will inevitably develop disease escape with time. Upon the development of castration-resistant prostate cancer, other androgen-axis-targeted treatments may be added in an effort to starve the disease of its androgen signaling. Nevertheless, additional androgen-pathway resistance usually develops to these novel hormonal therapies. In this review, we will discuss the resistance mechanisms to modern androgen-axis modulators and how these alterations can influence a patient’s response to novel hormonal therapy. We conceptualize these resistance pathways as three broad categories: (1) reactivation of androgen/AR-signaling, (2) AR bypass pathways, and (3) androgen/AR-independent mechanisms. We highlight examples of each, as well as potential therapeutic approaches to overcome these resistance mechanisms.

Original languageEnglish (US)
Article number29
Pages (from-to)1-10
Number of pages10
JournalCurrent urology reports
Volume17
Issue number4
DOIs
StatePublished - Apr 1 2016

Keywords

  • Androgen receptor
  • Biomarker
  • Prostate cancer
  • Resistance
  • Splice variants

ASJC Scopus subject areas

  • Urology

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