For example, in WT GIST, an IGF2-IGF1R autocrine/paracrine loop sustained by overexpression of both the receptor and its ligand in the same tumor microenvironment [5,16,17,57,58] may activate a secondary autocrine/paracrine loop formed by KITLG and WT KIT leading to increased KIT phosphorylation (refs. 9,10,13 and present results) and cell proliferation. This evidence concerns the gene IGF1R and gastrointestinal stromal tumor.