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Ref Type Journal Article
PMID (29573334)
Authors Cha Y, Kim HP, Lim Y, Han SW, Song SH, Kim TY
Title FGFR2 amplification is predictive of sensitivity to regorafenib in gastric and colorectal cancers in vitro.
Journal Molecular oncology
Vol 12
Issue 7
Date 2018 06
Abstract Text Although regorafenib has demonstrated survival benefits in patients with metastatic colorectal and gastrointestinal stromal tumors, no proven biomarker has been identified for predicting sensitivity to regorafenib. Here, we investigated preclinical activity of regorafenib in gastric and colorectal cancer cells to identify genetic alterations associated with sensitivity to regorafenib. Mutation profiles and copy number assays of regorafenib target molecules indicated that amplification of fibroblast growth factor receptor 2 (FGFR2) was the only genetic alteration associated with in vitro sensitivity to regorafenib. Regorafenib effectively inhibited phosphorylation of FGFR2 and its downstream signaling molecules in a dose-dependent manner and selectively in FGFR2-amplified cells. Regorafenib induced G1 arrest (SNU-16, KATO-III) and apoptosis (NCI-H716); however, no significant changes were seen in cell lines without FGFR2 amplification. In SNU-16 mice xenografts, regorafenib significantly inhibited tumor growth, proliferation, and FGFR signaling compared to treatment with control vehicle. Regorafenib effectively abrogates activated FGFR2 signaling in FGFR2-amplified gastric and colorectal cancer and, therefore, might be considered for integration into treatment in patients with FGFR2-amplified gastric and colorectal cancers.


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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
Gene 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
FGFR2 amp colorectal cancer predicted - sensitive Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Stivarga (regorafenib) inhibited Fgfr2 signaling and proliferation of FGFR2-amplified colorectal cancer cells in culture (PMID: 29573334). 29573334
FGFR2 amp stomach cancer sensitive Regorafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Stivarga (regorafenib) inhibited Fgfr2 signaling and proliferation of FGFR2-amplified gastric cancer cell lines in culture, resulted in tumor growth inhibition in cell line xenograft models (PMID: 29573334). 29573334