Invited ReviewVascular endothelial growth factor (VEGF) and VEGF receptor inhibitors in the treatment of renal cell carcinomas
Graphical abstract
Section snippets
Clinical course of renal cell carcinomas
Tumors of the kidney arise from cells in its outer portion, or cortex, and from its inner portion, or medulla. Siegel et al. estimated that about 64,000 new cases of kidney cancer will be diagnosed in the United States in 2017 (41,000 men and 23,000 women) and 24,000 people will die of the disease (14,000 men and 10,000 women) [1]. Deaths from cancer of the kidney account for about 2.3% of all cancer-related mortalities in the United States. Symptoms which prompt a person with renal cell
An overview of new blood vessel formation
The circulation is required for transporting oxygen, nutrients, hormones, and growth factors to and the removal of carbon dioxide and catabolites from cells and organs [6]. New blood vessel formation, or neovascularization, is divided into vasculogenesis and angiogenesis. The former is the process of new blood vessel formation from angioblasts that occurs during embryonic development. The latter is the process of new blood vessel formation from pre-existing vasculature. Signaling by the VEGF
Structure of VEGFR2-drug complexes
Axitinib is an inhibitor of VEGFR1/2/3 protein-tyrosine kinases that is approved as a second-line treatment for metastatic renal cell carcinomas (Table 5). The X-ray structure shows that the NH group of the axitinib indazole scaffold (Fig. 7A) forms a hydrogen bond with the hinge E917 carbonyl group of VEGFR2 while the N2 nitrogen of the scaffold forms a second hydrogen bond with the NH group of the F918 [68]. Because the enzyme has the DFG-Dout conformation, the αC-E885 carboxylate is able to
Epilogue
Maharaj et al. surveyed the expression of VEGF-A and VEGFR2 in the adult mouse [106]. They found that VEGF-A is expressed in all vascularized organs and tissues. It was expressed in close proximity to fenestrated blood vessels within endocrine glands, the choroid plexus, and kidney glomeruli. Fenestrae are the small pores in endothelial cells that allow for the transfer of small molecules and proteins with the surrounding tissue. In general VEGF-A is not expressed by endothelial cells, but
Acknowledgments
The colored figures in this paper were checked to ensure that their perception was accurately conveyed to colorblind readers [111]. The author thanks Laura M. Roskoski for providing editorial and bibliographic assistance.
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