ABSTRACT
Introduction .................................................................................................... 2 Identification of VEGF .................................................................................. 4 Biological activities of VEGF-A ................................................................... 4 VEGF isoforms ............................................................................................... 5 Regulation of VEGF gene expression......................................................... 6
Oxygen tension.................................................................................. 6 Growth factors, hormones, and oncogenes .................................. 7
VEGF receptors .............................................................................................. 7 VEGFR-1 (Flt-1) ................................................................................. 8 VEGFR-2 (KDR, human; Flk-1, mouse)......................................... 9 Neuropilin (NRP)1 and NRP2 ...................................................... 10
Role of VEGF in physiological angiogenesis .......................................... 11 Role of VEGF in pathologic conditions ................................................... 12
Tumor angiogenesis........................................................................ 12 Preclinical studies............................................................. 12 Clinical trials of VEGF inhibitors in cancer patients.. 14
Intraocular neovascular syndromes............................................. 15 Perspectives................................................................................................... 16 References...................................................................................................... 17
Introduction The observation that tumor growth can be accompanied by increased vascularity was reported more than one century ago (for review, see Reference 1). In 1939, Ide et al. postulated the existence of a tumor-derived blood vessel growth stimulating factor on the basis of the observation that tumors transplanted in transparent chambers induced intense neovascular responses in the host.2 These authors proposed that such a factor might promote the development of a neovascular supply needed for delivery of nutrients to the growing tumor.2 In 1945, Algire et al. advanced this concept, hypothesizing that the rapid growth of tumor transplants is crucially dependent on the development of a neovascular supply.3 In 1971, Folkman proposed that anti-angiogenesis may be a valid strategy for treating human cancer, and a search for regulators of angiogenesis that may represent therapeutic targets began.4
