What is the meaning of notch pathway and how can we selectively do the targeting?

Abstract

Notch receptors participate in a highly conserved signaling pathway that regulates normal developmental and tissue homeostasis in a context-dependent manner. Deregulated Notch signaling is involved in numerous human diseases and recently, a substantial body of evidence has been generated in support of this pathway playing critical roles in several types of cancer. The finding that activating Notch-1 mutations are frequently found in patients suffering from T-cell acute lymphoblastic leukemia is one of the best examples, but an abnormal expression of different human Notch receptors also contributes to B-cell tumors as well as a number of solid cancers such as breast, colon, pancreas, brain, lung, skin and other tissues. Several γ-secretase inhibitors are currently being explored for their potential therapeutic applications in Notch-associated tumors. Alternative approaches involve the development of antibodies to inhibit Notch receptors, their activating ligands, or other components of the Notch pathway. In this book chapter, we review the rationale for Notch inhibition in cancer, the current state of the art, as well as potential strategies that try to target the oncogenic properties of Notch signaling.