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Infigratinib Mediates Vascular Normalization, Impairs Metastasis, and Improves Chemotherapy in Hepatocellular Carcinoma.
Huynh, Hung; Lee, Liek Yeow; Goh, Kah Yong; Ong, Richard; Hao, Huai-Xiang; Huang, Alan; Wang, Youzhen; Graus Porta, Diana; Chow, Pierce; Chung, Alexander.
Afiliación
  • Huynh H; Laboratory of Molecular Endocrinology, Division of Molecular and Cellular Research, National Cancer Centre, Singapore.
  • Lee LY; Laboratory of Molecular Endocrinology, Division of Molecular and Cellular Research, National Cancer Centre, Singapore.
  • Goh KY; Laboratory of Molecular Endocrinology, Division of Molecular and Cellular Research, National Cancer Centre, Singapore.
  • Ong R; Laboratory of Molecular Endocrinology, Division of Molecular and Cellular Research, National Cancer Centre, Singapore.
  • Hao HX; Novartis Institutes for Biomedical Research, Cambridge, MA.
  • Huang A; Novartis Institutes for Biomedical Research, Cambridge, MA.
  • Wang Y; Oncology Drug Discovery Pharmacology, Novartis Institutes for Biomedical Research, Cambridge, MA.
  • Graus Porta D; Oncology Translational Research, Novartis Institutes for Biomedical Research at Basel, Basel, Switzerland.
  • Chow P; Department of General Surgery, Singapore General Hospital, Singapore.
  • Chung A; Department of General Surgery, Singapore General Hospital, Singapore.
Hepatology ; 69(3): 943-958, 2019 03.
Article en En | MEDLINE | ID: mdl-30575985
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos de Fenilurea / Pirimidinas / Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Hepatology Año: 2019 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos de Fenilurea / Pirimidinas / Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Hepatology Año: 2019 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Estados Unidos