Notch Antagonists- Potential Modulators of Cancer and Inflammatory Diseases

Notch is a key player in various developmental
processes during the embryonic stage as well as in regulating
tissue homeostasis, cell differentiation, and stem cell maintenance
in adult life. Activation of Notch signaling occurs following
Notch receptor−ligand interaction and subsequent enzymatic
proteolysis by the gamma-secretase complex, resulting in the
cytoplasmic release of a Notch intracellular domain, which
translocates to the nucleus to initiate the downstream transcrip-
tional machinery. Notch activation and its aberrant signaling have
been broadly linked to the pathogenesis of cancer and some
chronic inflammatory diseases resulting in pathologic fibrotic
processes. This review focuses on the molecular basis of Notch-
induced signaling and its interaction with other pathways to
identify therapeutic targets. We also highlight current efforts to pharmacologically intervene in Notch signaling and discuss promising ongoing experimental and clinical studies.