NOTCH1 and neoplasm: The lack of predictive biomarkers for patient selection, the fact that Val1744 is not a good marker for Notch activity as Val1744 levels do not necessarily correlate with Notch1 activity [83], the sparse availability of robust pharmacological markers to monitor on-target activity [137], and the pleiotropic effect of current pan-Notch inhibitors targeting multiple Notch family members (both with GSI, as well as, ligand neutralization) lead to low anti-tumor activity and dose-limiting toxicities in normal tissues.