NOTCH Decoys That Selectively Block DLL/NOTCH or JAG/NOTCH Disrupt Angiogenesis by Unique Mechanisms to Inhibit Tumor Growth

Abstract

This is the first report identifying unique regions of the NOTCH1 extracellular domain that interact with JAG-class and DLL-class ligands. Using this knowledge, we developed therapeutic agents that block JAG-dependent NOTCH signaling and demonstrate for the first time that JAG blockade inhibits experimental tumor growth by targeting tumor angiogenesis.