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. The gene discussed is NOTCH1; the disease is neoplasm.