Top NOTCH targets: notch signaling in cancer

The evolutionarily conserved Notch signaling pathway controls diverse events such as cell fate determination, proliferation, apoptosis, and stem cell maintenance. Dysregulation of this pathway has been implicated as a causative event in multiple cancers, including T-cell acute lymphoblastic leukemia (T-ALL), where mutation of Notch1 occurs in >50% of patients. Although mutation has not been observed in solid tumors, changes in expression of ligands and receptors, as well as pathway modulators, may play a role in pathogenesis. More recent evidence suggests that Notch signaling is also critical in tumor angiogenesis. We review the data that support the development of therapeutics to target the Notch pathway for the treatment of cancer. Drug Dev Res 69:319–328, 2008. © 2008 Wiley-Liss, Inc.