VEGFA and neoplasm: The central region of the spheroid becomes necrotic, with a surrounding layer of cells whose hypoxia triggers a cascade of hypoxia-inducible factor-1 (HIF-1) and vascular-endothelial-growth-factor (VEGF)-mediated signaling events that initiate tumor vascularization by promoting growth and extension (angiogenesis) of nearby blood vessels [2].