Alterations in NOTCH signaling pathways have been reported in up to 33.4% of ESCCs; in particular, the SMGs NOTCH1, NOTCH3 and FBXW7 are mutated in 16%, 6% and 5% of ESCC, respectively [26,32,33]. This evidence concerns the gene FBXW7 and esophageal squamous cell carcinoma.