Because of the pivotal role of HER2 in esophageal carcinogenesis and the possibility of heterodimers formation between IGF1R and HER2, we suggest that a cross talk between the ErbB/HER family and IGF1R signaling pathway could sustain IGF1R activation and down-stream p-ERK1/2 mediated proliferation, in particular in hyperinsulinemic MKR mice in which IGF1R is highly expressed even in absence of lesions, and in which the higher insulin concentration induces cancer cell HER2 over-expression (Figure 8). This evidence concerns the gene EGFR and cancer.