Thus, our data uncovers the novel mechanism of the cross-talk between FGFR- and VEGFR- mediated cascades in IM-resistant GISTs lacking secondary KIT mutations and suggests that the dual blockade of the aforementioned signaling pathways might be an effective treatment strategy for patients with GIST that acquired resistance to IM via KIT-independent mechanisms. This evidence concerns the gene KIT and gastrointestinal stromal tumor.