Abstract
Vascular endothelial growth factors (VEGFs) belong to the platelet-derived growth factor supergene family, and they play central roles in the regulation of angiogenesis and lymphangiogenesis. VEGF-A, the major factor for angiogenesis, binds to two tyrosine kinase (TK) receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1), and regulates endothelial cell proliferation, migration, vascular permeability, secretion and other endothelial functions. VEGFR-2 exhibits a strong TK activity towards pro-angiogenic signals, whereas the soluble VEGFR-1 (sFlt-1) functions as an endogenous VEGF inhibitor. sFlt-1 is abnormally overexpressed in the placenta of preeclampsia patients, resulting in the major symptoms of the disease due to abnormal trapping of VEGFs. The VEGF-VEGFR system is crucial for tumour angiogenesis, and anti-VEGF-VEGFR molecules are now widely used in the clinical field to treat cancer patients. The efficacy of these molecules in prolonging the overall survival of patients has been established; however, some cancers do not respond well and reduced tumour sensitivity to anti-VEGF signals may occur after long-term treatment. The molecular basis of tumour refractoriness should be determined to improve anti-angiogenic therapy.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Angiogenesis Inhibitors / pharmacology
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Angiogenesis Inhibitors / therapeutic use
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Animals
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Female
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Humans
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Lymphangiogenesis
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Male
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Molecular Targeted Therapy
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / chemistry
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Neoplasm Proteins / metabolism
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Neoplasms / drug therapy
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Neoplasms / metabolism
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Neovascularization, Pathologic / drug therapy
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Neovascularization, Pathologic / metabolism*
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Neovascularization, Physiologic*
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Pre-Eclampsia / drug therapy
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Pre-Eclampsia / metabolism
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Pregnancy
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Signal Transduction* / drug effects
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Vascular Endothelial Growth Factor A / antagonists & inhibitors
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Vascular Endothelial Growth Factor A / chemistry
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Vascular Endothelial Growth Factor A / metabolism*
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Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors
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Vascular Endothelial Growth Factor Receptor-1 / chemistry
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Vascular Endothelial Growth Factor Receptor-1 / metabolism*
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Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
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Vascular Endothelial Growth Factor Receptor-2 / chemistry
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Vascular Endothelial Growth Factor Receptor-2 / metabolism*
Substances
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Angiogenesis Inhibitors
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Neoplasm Proteins
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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FLT1 protein, human
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Vascular Endothelial Growth Factor Receptor-1
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Vascular Endothelial Growth Factor Receptor-2