Saracatinib impairs the peritoneal dissemination of diffuse-type gastric carcinoma cells resistant to Met and fibroblast growth factor receptor inhibitors.
Bottom Line: Saracatinib also effectively impaired peritoneal dissemination of Met-independent and FGFR2-independent SGC cells.Moreover, DGC cell lines exhibited nearly mutually exclusive susceptibility to Met, FGFR and Src inhibitors.These results suggest that DGC have distinct sensitivities to molecular target drugs and that targeting Src is beneficial in the treatment of DGC insensitive to Met and FGFR inhibition.
Affiliation: Division of Metastasis and Invasion Signaling, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.Show MeSH
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Mentions: The effects of several inhibitors targeted to signaling molecules other than Met were then examined. PD-173074, a pan-FGFR inhibitor, treatment strongly inhibited the growth of KATO-III and HSC-39 and moderately inhibited HSC-43 and HSC-64 (Fig.3a). These sensitive cell lines displayed increased phosphorylation of FRS2α, an adaptor protein for FGFR (Fig.3b). KATO-III and HSC-43 cells also showed robust overexpression and phosphorylation of FGFR2α, which is consistent with k-sam amplification in those cell lines.36 It is unclear why FGFR2α expression was not detected in HSC-39 cells, which also have k-sam amplification.36 Taken together, phosphorylation of FRS2α and overexpression of FGFR2α seem to be correlated with sensitivity to FGFR inhibition.
Affiliation: Division of Metastasis and Invasion Signaling, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.