Infigratinib mediates vascular normalization, impairs metastasis and improves chemotherapy in hepatocellular carcinoma

Abstract

The fibroblast growth factor (FGF) signaling cascade is a key signaling pathway in hepatocarcinogenesis. We report high FGFR expression in 17.7% (11 of 62) of HCC models. Infigratinib, a pan‐FGFR inhibitor, potently suppresses the growth of high‐FGFR‐expressing and Sorafenib‐resistant HCCs. Infigratinib inhibits FGFR signaling and its downstream targets, cell proliferation, the angiogenic rescue program, hypoxia, invasion and metastasis. Infigratinib also induces apoptosis and vessel normalization and improves the overall survival of mice bearing FGFR‐driven HCCs. Infigratinib acts in synergy with the microtubule‐depolymerizing drug Vinorelbine to promote apoptosis, suppress tumor growth and improve the overall survival of mice. Increased expression levels of FGFR‐2 and FGFR‐3 via gene amplification correlate with treatment response and may serve as potential biomarkers for patient selection. Conclusion Treatments with Infigratinib alone or in combination with Vinorelbine may be effective in a subset of HCC patients with FGFR‐driven tumors.

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