Vascular endothelial growth factor: regulation in the mouse skin carcinogenesis model and use in antiangiogenesis cancer therapy.
Of the various mechanisms responsible for tumor neovascularization, the angiogenesis process, in particular vascular endothelial growth factor (VEGF), is described here as a target for cancer therapy. While hypoxia is a trigger of tumor angiogenesis, various alterations in oncogenes and tumor suppressor genes also have been reported to induce VEGF expression in tumors. The regulation of VEGF has been investigated in chemically induced mouse squamous cell carcinoma of the skin. In this cancer model, VEGF expression appears to be dependent on ras oncogene activation as well as the epidermal growth factor receptor. Thus, in addition to VEGF, oncogene signaling pathways may be relevant targets in antiangiogenesis cancer therapies. The central role of VEGF in angiogenesis has led to the development of several drugs targeting the pathway of this growth factor. The present paper provides an overview of these drugs and their stage of development. In the near future, clinical trials using anti-VEGF drugs and other antiangiogenic agents, such as endostatin and angiostatin, will yield valuable information about their potential for cancer therapy.
Conti
Claudio J
CJ
Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas 78957, USA. sa83125@odin.mdacc.tmc.edu
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008222:Lymphokines / Q000378:metabolism*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D018631:ras Proteins / Q000378:metabolism
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D018631:ras Proteins