FGFR2扩增在5%-10%的胃癌中发现，主要出现在侵袭性弥漫性亚型中[1，2]。畸变与其他受体酪氨酸激酶扩增(ERBB2,MET)[2]是相互排斥的。在体外，FGFR2扩增的胃癌细胞株对FGFR TKIs[3]的生长抑制作用选择性敏感。FGFR2下调导致细胞生长和存活显著抑制，进一步转化为体内肿瘤生长衰退[4-6]。靶向依赖性的其他证据来自抗FGFR2单克隆抗体治疗的异种移植模型，该模型在活化的FGFR2信号驱动下对胃癌表现出强有力的抗肿瘤活性[7，8]。
- Matsumoto K, Arao T, Hamaguchi T et al. FGFR2 gene amplification and clinicopathological features in gastric cancer. Br J Cancer 2012; 106: 727–732.
- Deng N, Goh LK, Wang H et al. A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets. Gut 2012; 61: 673–684.
- Kunii K, Davis L, Gorenstein J et al. FGFR2- amplified gastric cancer cell lines require FGFR2 and Erbb3 signaling for growth and survival. Cancer Res 2008; 68: 2340–2348.
- Takeda M, Arao T, Yokote H et al. AZD2171 shows potent antitumor activity against gastric cancer over-expressing fibroblast growth factor receptor 2/keratinocyte growth factor receptor. Clin Cancer Res 2007; 13: 3051–3057.
- Gozgit JM, Wong MJ, Moran L et al. Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer models. Mol Cancer Ther 2012; 11: 690–699.
- Guagnano V, Kauffmann A, Wöhrle S et al. FGFR genetic alterations predict for sensitivity to NVP-BGJ398, a selective pan-FGFR inhibitor. Cancer Discov 2012; 2: 1118–1133.
- Zhao WM, Wang L, Park H et al. Monoclonal antibodies to fibroblast growth factor receptor 2 effectively inhibit growth of gastric tumor xenografts. Clin Cancer Res 2010; 16: 5750–5758.
- Bai A, Meetze K, Vo NY et al. GP369, an FGFR2-IIIb-specific antibody, exhibits potent antitumor activity against human cancers driven by activated FGFR2 signaling. Cancer Res 2010; 70: 7630–7639.
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