Targeting FGFR1 enhances olaparib sensitivity via MAPK-mediated BRCA2 downregulation in mCRPC.

ABSTRACT:

Background

Olaparib has demonstrated therapeutic potential in treating metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) gene mutations, especially BRCA2. However, resistance to PARP inhibition remains a significant clinical hurdle. Recent evidence suggests frequent activation of fibroblast growth factor receptor 1 (FGFR1) signaling in mCRPC, yet its impact on DNA repair regulation is poorly understood. This study aimed to investigate whether FGFR1 signaling modulates BRCA2 expression and contributes to PARP inhibitor resistance.

Methods

We performed integrative transcriptomic analyses of multiple mCRPC datasets to examine the correlation between FGFR1 and BRCA2 expression. Functi

SUBMITTER: Chen J 

PROVIDER: S-EPMC12603815 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature