Homing in on a Moving Target: Androgen Receptor Cistromic Plasticity in Prostate Cancer

Abstract

The androgen receptor (AR) is the critical driver in prostate cancer and exerts its function mainly through transcriptional control. Recent advances in clinical studies and cell line models have illustrated that AR chromatin binding features are not static; rather they are highly variable yet reproducibly altered between clinical stages. Extensive genomic analyses of AR chromatin binding features in different disease stages have revealed a high degree of plasticity of AR chromatin interactions in clinical samples. Mechanistically, AR chromatin binding patterns are associated with specific somatic mutations on AR and other permutations, including mutations of AR-interacting proteins. Here we summarize the most recent studies on how the AR cistrome is dynamically altered in prostate cancer models and patient samples, and what implications this has for the identification of therapeutic targets to avoid the emergence of treatment resistance.

Trial registration: ClinicalTrials.gov NCT03568656 NCT05488548.

Keywords: androgen receptor; cistromic plasticity; epigenetics; prostate cancer.