ArticleCell death discovery2025
FGF1-FGFR2 axis regulated by nuclear receptor RORγ represents an effective strategy in intrahepatic cholangiocarcinoma.
Article in Cell death discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
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 fibroblast growth factor 1 (FGF1) expression and secretion, which in turn activated FGFR2. Inhibition of RORγ markedly decreased FGF1 levels in conditioned media, whereas exogenous FGF1 restored tumor growth. Notably, RORγ antagonists synergized with pemigatinib to overcome resistance in pemigatinib-refractory models. Collectively, these findings identify the RORγ-FGF1-FGFR2 axis as a critical oncogenic driver in iCCA and highlight RORγ inhibition as a promising therapeutic strategy to suppress tumor progression and enhance sensitivity to FGFR inhibitors.
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Registered trials
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