Interplay Between Genomic Alterations and Androgen Receptor Signaling During Prostate Cancer Development and Progression

Michael D. Nyquist, Scott M. Dehm

Research output: Contribution to journalReview articlepeer-review

34 Scopus citations

Abstract

Advanced prostate cancer (PCa) treated with androgen deprivation therapy (ADT) eventually relapses to an ADT-resistant disease referred to as castration-resistant PCa (CRPC). Recent integrative analyses of PCa genomes have led to the elucidation of potential subtypes that are revelatory to the development of PCa as well as the mechanisms of resistance to ADT and CRPC progression. These studies have confirmed that alterations in the androgen receptor (AR) signaling axis are central to CRPC progression, and have uncovered complex mechanisms by which AR and other components of the AR signaling axis affect, and are affected by, genomic changes and epigenetic transformations. Among the most frequent alterations in CRPC are direct alterations in the AR gene. These AR gene alterations include AR amplification, point mutations, and more recently AR gene rearrangements leading to expression of truncated, constitutively active AR splice variants that are impervious to ADT. In this review, we will highlight genomic alterations that are important for development and progression of PCa, with a focus on how these alterations affect, and are affected by, activity of the AR signaling axis.

Original languageEnglish (US)
Pages (from-to)61-69
Number of pages9
JournalHormones and Cancer
Volume4
Issue number2
DOIs
StatePublished - Apr 2013

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