Notch pathway has been reported to have both oncogenic and tumor suppressor roles, dependent on the cancer cell type. It is an evolutionally conserved signaling pathway, consisting a family of transmembrane receptors. These notch receptors will communicate and regulate other cells, which have a specific ligand for their receptors. This highly coordinated signaling system controls many aspects of cell biology including differentiation, proliferation and death.
Notch-2 gene mutation causes deregulation of the signaling pathways such as notch2 receptor and IL-2 receptor (Toll- like receptor) these will lead to increased activation of nuclear factor kappa B (NFκB), which leads to increased survival of malignant cells.
The notch inhibitors in malignant cells have the potential to slow cell proliferation, cause apoptosis and induce differentiation. These effects are surprisingly given an extensive cross- through of notch with major malignant pathways such as NFκB, Ras and Akt. Notch pathway is a particularly powerful target of tumor stem cell subsets, that is resistant to standard therapy