FGFR2 amplification in gastric and colon cancer cell lines is associated with response to NVP-BGJ398. FGFR2 amplification in gastric and colon cancer cell.

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FGFR2 amplification in gastric and colon cancer cell lines is associated with response to NVP-BGJ398. FGFR2 amplification in gastric and colon cancer cell lines is associated with response to NVP-BGJ398. A, box-plot showing FGFR2 copy number expressed as log2 ratio for the 541 cell lines grouped according to cancer type. B, scatter plot of gastric and large intestine cancer cell lines showing the correlation between FGFR2 DNA copy number and transcript expression. C, effect of NVP-BGJ398 on FGFR downstream signaling as measured by FRS2 Tyr-phosphorylation and Erk1/2 activation. α-Actinin and total Erk1/2 protein levels are shown as a loading control. D, SNU16 tumor xenograft–bearing nude rats received NVP-BGJ398 at the indicated doses or vehicle for 14 consecutive days (n = 6 per group). The changes over time in tumor volume are shown. Statistical analysis was conducted by 1-way ANOVA–Dunnett versus vehicle control (*, P < 0.001). E, tumor tissues were recovered 3 and 24 hours after dose treatment and analyzed for FGFR2 Tyr-phosphorylation by Western blot analysis. Total FGFR2 Western blot analysis was conducted to monitor equal loading. Pharmacodynamic analysis of tumors treated with 15 mg/kg NVP-BGJ398 was not feasible due to insufficient material. Br, breast; Ch, chondrosarcoma; Co, colorectal; En, endometrial; Es, esophagus; Ew, Ewing sarcoma; Ga, gastric; Gl, glioma; HL, hematopoietic and lymphoid tissue; HN, head and neck; Ki, kidney; Li, liver; Lu, lung; Me, melanoma; Ms, mesothelioma; Nb, neuroblastoma; Os, osteosarcoma; Ov, ovarian; Pa, pancreas; Th, thyroid; UT, urinary tract. Vito Guagnano et al. Cancer Discovery 2012;2:1118-1133 ©2012 by American Association for Cancer Research