A half-century of VEGFA: from theory to practice

Identifying a blood vessel growth factor The discovery of the potent angiogenic factor VEGFA and the subsequent studies that led to the development and successful translation of VEGF inhibitors into the clinic illustrate the invaluable role physician-scientists play in advancing human health. In 1972, pediatric surgeon and cancer pioneer Judah Folkman published an editorial in the New England Journal of Medicine, where he introduced the concept of antiangiogenic therapy to slow the growth of solid tumors (1). Based on work performed in his own laboratory and clinical observation, he had isolated a tumor angiogenic factor (TAF) that promoted endothelial cell proliferation and neovascularization. Folkman, in collaboration with pathologist Hal Dvorak, also recognized the importance of vascular permeability with ensuing extravascular clotting to lay down the necessary tumor stroma to support angiogenesis and tumor growth and metastasis, and the two began their quest to identify the vascular permeability factor (VPF) (2). To accomplish this, tumor cells were cultured in serum-free media and supernatants were tested for the presence of a vascular permeability–inducing factor(s) secreted by the cells (3, 4). They soon found that several tumor types possessed this vascular permeability–promoting activity, and they went on to successfully isolate the factor, demonstrating that VPF was 50,000 times more potent than histamine on a molar basis.