VEGF and PDGF Receptors: Biologic Relevance and Clinical Approaches to Inhibition

The dependence of tumor growth on the development of a neovasculature is well established. One of the best studied angiogenic factor is vascular endothelial growth factor (VEGF). VEGF belongs to a family of homodimeric glycoproteins that bind to three different VEGF receptor (VEGFR) tyrosine kinases in an overlapping pattern. VEGFRs share regulatory mechanisms with other well-characterized receptor tyrosine kinases, such as the platelet-derived growth factor receptor (PDGFR). These mechanisms include receptor dimerization and activation of tyrosine kinase, as well as creation of docking sites for signal transducers to direct cellular function including cell migration, survival, and proliferation. Tumor biology studies, drug development, and clinical studies have established VEGFR and PDGFR as validated drug targets. Well-interconnected preclinical and clinical efforts are necessary for the continued development of this exciting process. This chapter will review the biological role of VEGFR and PDGFR signal transduction and the interplay between the different receptors as it relates to kidney cancer.