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Aberrant fibroblast growth factor (FGF) signaling plays a pivotal role in hepatocellularcarcinoma (HCC). Erdafitinib, a selective pan-FGFR tyrosine kinase inhibitor, hasshown efficacy in multiple cancers. This study demonstrates that erdafitinib exertspotent antitumor effects in HCC through dual induction of DNA damage andmitochondria-mediated apoptosis. In vitro, erdafitinib dose-dependently inhibited HCCcell proliferation and suppressed FGFR phosphorylation and downstream FRS2-ERKsignaling. Transcriptomic profiling identified significant enrichment of MAPK andPI3K/AKT signaling and mitochondrial apoptosis pathways. Mechanistically, erdafitinibtriggered a Bax/Bcl-2 imbalance, mitochondrial membrane potential dissipation, andcaspase-3 activation, culminating in apoptotic cell death. Concurrently, erdafitinibinduced oxidative stress-mediated DNA damage (γH2AX foci formation) and G2/M cellcycle arrest while impairing cell migration and invasion capacity. In vivo, erdafitinib (10-20 mg/kg) significantly suppressed tumor growth in xenograft models withoutdetectable toxicity. In summary, erdafitinib simultaneously targets proliferativesignaling, apoptotic machinery, and DNA stability in HCC, supporting its clinicalevaluation in FGFR-driven liver malignancies.