Important, the knockdown of <i>FGFR2</i>, and, in much less content, <i>FGF-2</i>, abrogated BGJ 398's activity against GIST-R2 cells both in vitro and in vivo, thereby illustrating the FGF-2/FGFR2-signaling axis in IM-resistant GISTs as a primary molecular target for this RTKi. This evidence concerns the gene FGFR2 and gastrointestinal stromal tumor.