WCLC 2025 - Posters & ePosters-P2.02.22 Analysis of FGF19 in Lung Squamous Cell Cancer Tissue and Cell Models

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This study investigated fibroblast growth factor 19 (FGF19) and its receptor FGFR4 in lung squamous cell carcinoma (SCC), a subtype of non-small cell lung cancer. While previous research in Chinese patient cohorts identified FGF19 gene amplification as an oncogenic driver, the current analysis of Central European SCC samples and cell lines revealed no FGF19 genomic amplification. Despite this, elevated FGF19 protein secretion was observed in tumor specimens and cell models, indicating that increased FGF19 levels do not necessarily depend on gene amplification.<br /><br />The study assessed the sensitivity of a panel of SCC cell lines to two inhibitors: BLU9931 (selective FGFR4 inhibitor) and Erdafitinib (pan-FGFR inhibitor). Both inhibitors showed dose-dependent growth inhibition in 2D cell culture. A strong correlation was noted between the sensitivities to the two drugs. However, when tested in 3D spheroid models, the inhibitors had minimal effects on spheroid formation and growth, suggesting reduced efficacy in this more physiologically relevant model.<br /><br />Importantly, neither the FGF19 gene dose nor the levels of secreted FGF19 protein correlated significantly with sensitivity to either inhibitor. This indicates that genomic FGF19 status and protein secretion alone are not reliable predictive biomarkers for FGFR inhibitor response in SCC.<br /><br />In conclusion, FGF19 gene amplification is uncommon in Central European lung SCC patients, unlike reports from other populations. Although FGFR inhibitors effectively reduce SCC cell viability in 2D, their impact in 3D models is limited. The lack of correlation between FGF19 gene dose or protein secretion and drug sensitivity suggests that additional factors influence response to FGFR-targeted therapies in SCC. These findings highlight the need for further research to identify predictive biomarkers and optimize FGFR inhibitor use in this cancer subtype.

Asset Subtitle

Lukas Koszik

Meta Tag

Speaker Lukas Koszik

Topic Tumor Biology – Preclinical Biology

Keywords

FGF19

FGFR4

lung squamous cell carcinoma

non-small cell lung cancer

gene amplification

FGFR inhibitors

BLU9931

Erdafitinib

2D vs 3D cell culture

biomarkers for drug sensitivity