Notch signaling drives stemness and tumorigenicity of esophageal adenocarcinoma.

[esophageal adenocarcinoma]

Esophageal adenocarcinoma ranks sixth in cancer mortality in the world and its incidence has risen dramatically in the Western population over the last decades . Data presented herein strongly suggest that Notch signaling is critical for esophageal adenocarcinoma and underlies resistance to chemotherapy . We present evidence that Notch signaling drives a cancer stem cell phenotype by regulating genes that establish stemness . Using patient-derived xenograft models , we demonstrate that inhibition of Notch by gamma-secretase inhibitors (GSI ) is efficacious in downsizing tumor growth . Moreover , we demonstrate that Notch activity in a patient 's ultrasound-assisted endoscopic-derived biopsy might predict outcome to chemotherapy . Therefore , this study provides a proof of concept that inhibition of Notch activity will have efficacy in treating esophageal adenocarcinoma , offering a rationale to lay the foundation for a clinical trial to evaluate the efficacy of GSI in esophageal adenocarcinoma treatment . Cancer Res ; 74 (21 ); 6364 -74 . ©2014 AACR .