Tumor angiogenesis, the process of new blood vessel formation from pre-existing vessels, is critical for tumor growth and metastasis.138 Cytokines, chemokines, and growth factors, including VEGF, PDGF, and IL-8 by HNSCC cells and stromal cells, activate endothelial cells and induce angiogenesis.131 In particular, the interaction of endothelial and HNSCC cells triggers the NOTCH-1 signaling pathway and promotes capillary tubule formation. This evidence concerns the gene NOTCH1 and neoplasm.