Authors
Songyan Qi, Scott M Dehm
Published in
Endocrinology. Jun 17, 2026. Epub Jun 17, 2026.
Abstract
Prostate cancer development and progression depend on androgen receptor (AR) signaling. Therefore, androgen-deprivation therapy (ADT) and AR signaling inhibitors (ARSIs) are standard therapies for advanced or metastatic disease. Although these treatments are initially effective, prostate cancer inevitably progresses to a lethal stage termed castration-resistant prostate cancer (CRPC). In the majority of patients, CRPC occurs via re-activation of AR signaling (CRPC-AR). However, lineage plasticity is a hallmark of cancer that drives AR-independent CRPC phenotypes in a subset of patients. One subtype of AR-negative CRPC is neuroendocrine prostate cancer (NEPC), which transforms from CRPC-AR by losing the characteristic AR-driven luminal epithelial identity and gaining neuroendocrine identity. Another AR-negative CRPC subtype lacks AR and neuroendocrine features and has therefore been classified as double-negative prostate cancer (DNPC). Chromatin modifications, alterations in three-dimensional (3D) genome structure, and expression of transcriptional regulators are crucial for controlling lineage states and modulating AR-dependent and AR-independent phenotypes in CRPC. Here, we highlight how high-resolution investigations of the 3D genome have revealed interdependence between chromatin architecture and transcriptional regulation, offering novel insights into the mechanisms of CRPC progression and context-specific targets for therapeutic intervention.
PMID:
42306870
Bibliographic data and abstract were imported from PubMed on 17 Jun 2026.
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