NOTCH3 and neoplasm: For instance, non-canonical activation of Notch1 protein sustained the proliferation of melanoma cells, while non-canonical Notch3 signaling could trigger endothelial cell apoptosis to restrict tumor angiogenesis.52,53 These non-classical mechanisms allow evolutionarily conserved Notch signaling to carry out more specific functions and may uncover new therapeutic targets as additional mechanisms are revealed in cancers.