FGF1-FGFR2 axis regulated by nuclear receptor RORγ represents an effective strategy in intrahepatic cholangiocarcinoma.

ABSTRACT: Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive malignancy with limited therapeutic options. Although targeted therapies like pemigatinib provide partial clinical benefits, acquired resistance remains a significant challenge. Through integrative bioinformatics analysis of public datasets and immunohistochemical validation, we identified the retinoid-related orphan receptor gamma (RORγ) as markedly upregulated in iCCA. Genetic silencing and pharmacological inhibition of RORγ (GSK805/XY101) suppressed proliferation, induced apoptosis in vitro, and significantly reduced xenograft tumor growth in vivo. Mechanistically, RORγ promoted fibroblast growth factor receptor 2 (FGFR2) signaling via two complementary mechanisms: direct transcriptional activation of FGFR2 and induction of f

SUBMITTER: Gu Z 

PROVIDER: S-EPMC12722201 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature