Targeting Notch in cancer with gamma-secretase inhibitors

C236 Gamma-secretase inhibitors are being evaluated for the treatment of cancers in which the Notch pathway has been activated. Inhibition of gamma-secretase activity prevents cleavage of the Notch receptor and release of the Notch Intracellular Domain, which regulates Notch-dependent gene expression. In vitro and in vivo models of T-ALL and other solid tumors have been developed to explore the mechanism of action of gamma-secretase inhibitors and to study the correlation pathway inhibition and anti-tumor efficacy.