Vascular endothelial growth factor as a therapeutic target in cancer.
OBJECTIVE
The role of vascular endothelial growth factor (VEGF) in angiogenesis, vascular maintenance, lymphangiogenesis, and immune cell function will be explained. The link between angiogenesis and tumor progression and the rationale for targeting VEGF in the treatment of cancer will be discussed. In addition, the various therapeutic approaches to inhibiting VEGF will be reviewed.


CONCLUSIONS
Advances in our understanding of the mechanisms underlying tumor progression have translated into a number of novel, biologically-based therapeutic strategies. One approach stems from evidence suggesting that angiogenesis is required for tumor growth and metastasis. While the vasculature is normally quiescent in adults, bursts of angiogenesis are tightly regulated by dozens of stimulatory and inhibitory factors. VEGF is thought to be the most potent direct-acting stimulatory regulator of angiogenesis. Excessive expression of VEGF is found in many types of cancer, and high levels correlate with increased microvascular density, disease recurrence, and decreased survival.


CONCLUSIONS
Inhibiting VEGF appears to be a valid therapeutic strategy and may prevent the growth of new tumor blood vessels, cause regression of the existing tumor vasculature, enhance the anti-tumor immune response, and normalize the vasculature (thereby improving the delivery of chemotherapy).
Bergsland
Emily K
EK
University of California-San Francisco Comprehensive Cancer Center, 1600 Divisidero, 4th Floor, San Francisco, CA 94115, USA. emilyb@medicine.ucsf.edu
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D042583:Lymphangiogenesis / Q000502:physiology; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000276:immunology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000502:physiology*
D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor