Vascular endothelial growth factor in human colon cancer: biology and therapeutic implications.
Tumor growth and metastasis are dependent on angiogenesis. Vascular endothelial growth factor (VEGF) plays an important role in the angiogenesis of numerous solid malignancies including colon cancer. Evidence from preclinical and clinical studies indicates VEGF is the predominant angiogenic factor in human colon cancer and is associated with formation of metastases and poor prognosis. Based on these results, it was hypothesized that inhibition of VEGF receptor activity could inhibit colon cancer liver metastasis. To test this hypothesis, the authors evaluated the ability of a small molecule inhibitor specific for the tyrosine kinase VEGF receptor Flk-1/KDR (SU5416) or multiple tyrosine kinase receptors (SU6668) to inhibit tumor angiogenesis and metastasis in a model of colon cancer hepatic metastasis. Both SU5416 and SU6668 inhibited metastases, microvessel formation, and cell proliferation while increasing tumor cell and endothelial cell apoptosis. These results showed that targeting the VEGF receptor/ligand system is a rational approach to inhibiting tumor growth and prolonging survival.
Ellis
L M
LM
University of Texas M.D. Anderson Cancer Center, Department of Surgical Oncology, Houston, Texas 77030, USA.
Takahashi
Y
Y
Liu
W
W
Shaheen
R M
RM
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000517:prevention & control / Q000556:secondary; D008222:Lymphokines / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000503:physiopathology; D011379:Prognosis; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors; D011975:Receptors, Mitogen / Q000037:antagonists & inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D007211:Indoles; D008222:Lymphokines; D020033:Protein Isoforms; D011758:Pyrroles; D017978:Receptors, Growth Factor; D011975:Receptors, Mitogen; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C116890:Semaxinib; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor