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Infigratinib Mediates Vascular Normalization, Impairs Metastasis, and Improves Chemotherapy in Hepatocellular Carcinoma
Author(s) -
Huynh Hung,
Lee Liek Yeow,
Goh Kah Yong,
Ong Richard,
Hao HuaiXiang,
Huang Alan,
Wang Youzhen,
Graus Porta Diana,
Chow Pierce,
Chung Alexander
Publication year - 2019
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.30481
Subject(s) - hccs , cancer research , fibroblast growth factor receptor , sorafenib , hepatocellular carcinoma , metastasis , fibroblast growth factor , angiogenesis , vinorelbine , epidermal growth factor receptor , medicine , oncology , cancer , receptor , cisplatin , chemotherapy
The fibroblast growth factor (FGF) signaling cascade is a key signaling pathway in hepatocarcinogenesis. We report high FGF receptor (FGFR) expression in 17.7% (11 of 62) of hepatocellular carcinoma (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 through 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 patients with HCC with FGFR‐driven tumors.