The dual role of the Notch signaling pathway in digestive system cancers

The Notch signaling pathway is critical for maintaining tissue homeostasis and plays dual roles in digestive system cancers, acting both as an oncogene and a tumor suppressor gene. This article explores its varied functions across esophageal, gastric, liver, pancreatic, and colorectal cancers. In esophageal and pancreatic cancers, Notch signaling may initially inhibit tumor growth but later promote progression, influenced by the primary cell types. In hepatocellular carcinoma, DLL4/Notch1 generally drives tumor growth, whereas Jag1/Notch2 tends to suppress tumor progression. In colon cancer, this pathway not only facilitates immune evasion but, in the presence of specific mutations, can also enhance the anti-tumor immune response. The functional complexity of Notch signaling presents significant therapeutic challenges, as broad-spectrum γ-secretase inhibitors (GSIs) are often associated with considerable side effects. Future treatment strategies should prioritize precision medicine, including subtype-specific Notch receptor inhibitors, biomarker-driven personalized therapies, and combination treatments aimed at modifying the tumor microenvironment. A thorough understanding of these dual roles is significant for developing more accurate and effective treatment approaches for digestive system cancers.