Targeting notch to eradicate pancreatic cancer stem cells for cancer therapy.

Pancreatic cancer is the most aggressive malignant disease once it is diagnosed and it remains the fourth leading cause of cancer-related death in the U.S.A. Recent data indicates that the Notch signaling pathway plays an important role in the development and progression of pancreatic cancer. Emerging evidence also suggests that the activation of the Notch signaling pathway is mechanistically associated with molecular characteristics of cancer stem cells (CSCs) in pancreatic cancer. Moreover, CSCs are known to be highly drug-resistant, suggesting that targeted inactivation of Notch signaling would be useful for overcoming drug resistance and the elimination of CSCs. This review describes the roles of the Notch signaling pathway in pancreatic cancer with a special emphasis on its novel functions in the regulation of pancreatic CSC. Moreover, the review also proposes that targeting the Notch signaling pathway by natural agents may represent a novel strategy for overcoming drug resistance and the elimination of CSCs, which would be useful for the successful treatment of patients diagnosed with pancreatic cancer.