The main angiogenesis downstream signal in HNC is usually mediated by VEGF-A and VEGFR-2; VEGF signaling can promote tumor cell proliferation, migration, immune system evasion, and cancer invasion (by activating key pathways such as the MAPK and PI3K–AKT), and can also play a role in chemotherapy resistance as it may induce autophagy that counteracts chemotherapy-induced stress [140,141]. This evidence concerns the gene VEGFA and cancer.