Ras regulation of vascular endothelial growth factor and angiogenesis.
Given the multifaceted role of Ras in tumor angiogenesis, pharmacologic targeting of such proteins may bring about at least three important consequences: (1) partial obliteration of the angiogenic competence of tumor cells, (2) an increase in vascular dependence and sensitization to apoptosis, and (3) a direct inhibition of endothelial cell responses to proangiogenic stimuli. Exploration of some of these possibilities, using various pharmacological compounds and antibodies, has already begun. An intriguing possibility is that Ras antagonists and signal transduction inhibitors may synergize with a number of other antiangiogenic modalities such as direct acting antiangiogenic agents (e.g., endostatin) or antivascular regimens involving low-dose continuous chemotherapy as a vasculature-targeting strategy.
Rak
J
J
Department of Medical Biophysics, Division of Cancer Biology Research, Sunnybrook Health Science Centre, University of Toronto, Toronto, Ontario M6G 2M9, Canada.
Kerbel
R S
RS
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008222:Lymphokines / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D018631:ras Proteins