The GR-LEDGF/p75-HSP27 Axis Contributes to Cross-Resistance Between Enzalutamide and Docetaxel in Prostate Cancer.

ABSTRACT: An emerging challenge in prostate cancer (PCa) treatment is the development of drug cross-resistance, wherein resistance to enzalutamide (ENZ), an androgen receptor signaling inhibitor (ARSI), also confers resistance to subsequent ARSI and docetaxel (DTX) treatments. The mechanisms underlying this drug cross-resistance remain unclear. Through RNA sequencing, we identified 93 overlapping differentially expressed genes (DEGs) in ENZ- and DTX-resistant PCa cells. Among the DEGs, HSPB1, which encodes heat shock protein 27 (HSP27), emerged as a key gene of interest. HSP27 is a known target of lens epithelium-derived growth factor p75 (LEDGF/p75), a transcription coactivator regulated by glucocorticoid receptor (GR). Both GR and LEDGF/p75 are overexpressed in advanced PCa and promote drug

SUBMITTER: Ochoa PT 

PROVIDER: S-EPMC12523889 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature