Preclinical data targeting vascular endothelial growth factor in colorectal cancer.
Vascular endothelial growth factor (VEGF) is the driving force behind angiogenesis in most solid malignancies. This also holds true for colorectal cancer (CRC), where increased levels of VEGF in primary cancers are associated with increased microvessel density and poor prognosis. These findings have led to preclinical studies evaluating the efficacy of anti-VEGF therapy in inhibiting the growth of CRC in ectopic and orthotopic locations. In preclinical models, numerous approaches to inhibit VEGF activity led to decreased tumor growth and angiogenesis. These studies led to clinical trials in which, unfortunately, single-agent anti-VEGF therapy was relatively ineffective for patients with metastatic CRC. However, combinations of anti-VEGF therapies with chemotherapy have clearly demonstrated clinical benefit. Understanding the mechanisms of the role of VEGF in CRC angiogenesis and the effect of anti-VEGF therapy on the tumor vasculature will allow oncologists to optimize therapeutic regimens targeting VEGF and its receptors.
Ellis
Lee M
LM
Department of Surgical Oncology, Box 444, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030-4009, USA. lellis@mdanderson.org
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D008113:Liver Neoplasms / Q000188:drug therapy / Q000503:physiopathology / Q000556:secondary*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000517:prevention & control; D012680:Sensitivity and Specificity; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects* / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A