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FGFR2 amplification is predictive of sensitivity to regorafenib in gastric and colorectal cancers in vitro.

FGFR2 amplification is predictive of sensitivity to regorafenib in gastric and colorectal cancers in vitro.
Author Information (click to view)

Cha Y, Kim HP, Lim Y, Han SW, Song SH, Kim TY,


Cha Y, Kim HP, Lim Y, Han SW, Song SH, Kim TY, (click to view)

Cha Y, Kim HP, Lim Y, Han SW, Song SH, Kim TY,

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Molecular oncology 2018 03 24() doi 10.1002/1878-0261.12194
Abstract

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 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. This article is protected by copyright. All rights reserved.

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