Vascular Endothelial Growth Factor: Basic Science and Clinical Progress
Napoleone Ferrara
Department of Molecular Oncology, Genentech, Inc., South San Francisco, California 94080
Correspondence: Address all correspondence and requests for reprints to: Napoleone Ferrara, M.D., Department of Molecular Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080. E-mail: nf{at}gene.com
Vascular endothelial growth factor (VEGF) is an endothelialcell-specific mitogen in vitro and an angiogenic inducer ina variety of in vivo models. Hypoxia has been shown to be amajor inducer of VEGF gene transcription. The tyrosine kinasesFlt-1 (VEGFR-1) and Flk-1/KDR (VEGFR-2) are high-affinity VEGFreceptors. The role of VEGF in developmental angiogenesis isemphasized by the finding that loss of a single VEGF alleleresults in defective vascularization and early embryonic lethality.VEGF is critical also for reproductive and bone angiogenesis.Substantial evidence also implicates VEGF as a mediator of pathologicalangiogenesis. In situ hybridization studies demonstrate expressionof VEGF mRNA in the majority of human tumors. Anti-VEGF monoclonalantibodies and other VEGF inhibitors block the growth of severaltumor cell lines in nude mice. Clinical trials with variousVEGF inhibitors in a variety of malignancies are ongoing. Veryrecently, an anti-VEGF monoclonal antibody (bevacizumab; Avastin)has been approved by the Food and Drug Administration as a first-linetreatment for metastatic colorectal cancer in combination withchemotherapy. Furthermore, VEGF is implicated in intraocularneovascularization associated with diabetic retinopathy andage-related macular degeneration.
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