Reference Detail

Ref Type Journal Article
PMID (19832844)
Authors Nakagawa T, Tohyama O, Yamaguchi A, Matsushima T, Takahashi K, Funasaka S, Shirotori S, Asada M, Obaishi H
Title E7050: a dual c-Met and VEGFR-2 tyrosine kinase inhibitor promotes tumor regression and prolongs survival in mouse xenograft models.
Journal Cancer science
Vol 101
Issue 1
Date 2010 Jan
URL
Abstract Text c-Met is the cellular receptor for hepatocyte growth factor (HGF) and is known to be dysregulated in various types of human cancers. Activation of the HGF/c-Met pathway causes tumor progression, invasion, and metastasis. Vascular endothelial growth factor (VEGF) is also known as a key molecule in tumor progression through the induction of tumor angiogenesis. Because of their key roles in tumor progression, these pathways provide attractive targets for therapeutic intervention. We have generated a novel, orally active, small molecule compound, E7050, which inhibits both c-Met and vascular endothelial growth factor receptor (VEGFR)-2. In vitro studies indicate that E7050 potently inhibits phosphorylation of both c-Met and VEGFR-2. E7050 also potently represses the growth of both c-met amplified tumor cells and endothelial cells stimulated with either HGF or VEGF. In vivo studies using E7050 showed inhibition of the phosphorylation of c-Met and VEGFR-2 in tumors, and strong inhibition of tumor growth and tumor angiogenesis in xenograft models. Treatment of some tumor lines containing c-met amplifications with high doses of E7050 (50-200 mg/kg) induced tumor regression and disappearance. In a peritoneal dissemination model, E7050 showed an antitumor effect against peritoneal tumors as well as a significant prolongation of lifespan in treated mice. Our results indicate that E7050 is a potent inhibitor of c-Met and VEGFR-2 and has therapeutic potential for the treatment of cancer.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
MET amp stomach cancer sensitive Golvatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Golvatinib (E7050) inhibited Met and Kdr (Vegfr2) phosphorylation, resulted in growth inhibition of gastric cancer cell lines in culture and in cell line xenograft models (PMID: 19832844). 19832844
Unknown unknown pancreatic cancer not applicable Golvatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Golvatinib (E7050) inhibited tumor angiogenesis and tumor growth in xenografts of a VEGF-overexpressing human pancreatic cancer cell line (PMID: 19832844). 19832844
MET amp lung cancer sensitive Golvatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Golvatinib (E7050) inhibited Met and Kdr (Vegfr2) phosphorylation, resulted in growth inhibition of lung cancer cells in culture and tumor regression in cell line xenograft models (PMID: 19832844). 19832844