IGF1R and hyperinsulinism: A pivotal role of IGF1R signaling in esophageal cancer onset in our animal model was first suggested by the high activation level of the IGF1R in dysplastic and cancer tissues of WT normoinsulinemic mice, suggesting that IGF1R is involved in duodenal reflux-dependent esophageal carcinogenesis even in the absence of hyperinsulinemia.