Predictive Biomarkers and Personalized Medicine FGFR 2 Gene Ampli fi cation in Gastric Cancer Predicts Sensitivity to the Selective FGFR Inhibitor AZD 4547

Liang Xie, XinyingSu,Lin Zhang,Xiaolu Yin,Lili Tang, Xiuhua Zhang,Yanping Xu, ZerenGao,Kunji Liu,Minhua Zhou, Beirong Gao,Danping Shen,Lianhai Zhang,Jiafu Ji,Paul R. Gavine,Jingchuan Zhang,Elaine Kilgour,Xiaolin Zhang,Qunsheng Ji

semanticscholar（2013）

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摘要

Purpose: FGFR gene aberrations are associated with tumor growth and survival. We explored the role of FGFR2 amplification in gastric cancer and the therapeutic potential of AZD4547, a potent and selective ATPcompetitive receptor tyrosine kinase inhibitor of fibroblast growth factor receptor (FGFR)1–3, in patients with FGFR2-amplified gastric cancer. Experimental Design: Array-comparative genomic hybridization and FISHwere used to identify FGFR2 amplification in gastric cancer patient tumor samples. The effects of FGFR2modulationwere investigated in gastric cancer cells with FGFR2 amplification and in patient-derived gastric cancer xenograft (PDGCX) models using two approaches: inhibition with AZD4547 and short hairpin RNA (shRNA) knockdown of

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