INSR and cancer: Even at levels of secreted IGF-II comparable to those observed in a subset of tumoral cells, the over-expression in IGF-II signal-transducing RTKs (namely IGF-IR and Insulin receptor fetal variant, up to six times the normal levels as shown in Figure 3) allows cancer cells to effectively respond to the secreted ligand signal in addition to the biological advantages provided by the cancer-specific IGF-II-secreted variant discussed herein and elsewhere [6,76].