title: Multitargeted receptor tyrosine kinase inhibition: an antiangiogenic strategy in non-small cell lung cancer.
abstract: In the United States, the leading cause of cancer-related deaths is lung cancer, of which more than 85% of cases are categorized as non-small cell lung cancer. The process of angiogenesis, which results in the formation of vasculature, is a complex and coordinated process that is required for cancer growth and metastasis. Pathways that promote angiogenesis have been targeted as a therapeutic approach in multiple types of cancer, including non-small cell lung cancer. Of these, the vascular endothelial growth factor pathway has been the most well studied, but more recently, the platelet-derived growth factor and fibroblast growth factor pathways have been identified as regulators of angiogenesis and potential mediators of resistance to vascular endothelial growth factor inhibition. Bevacizumab, a monoclonal antibody that binds to vascular endothelial growth factor, is currently the only antiangiogenic drug approved for the treatment of non-small cell lung cancer; however, several tyrosine kinase inhibitors that target vascular endothelial growth factor receptors as well as platelet-derived growth factor receptors and/or fibroblast growth factor receptors are being developed. This article reviews the role of the fibroblast growth factor and platelet-derived growth factor pathways in angiogenesis and provides a summary of dual (e.g., sorafenib, sunitinib) and triple (e.g., BIBF 1120, pazopanib) antiangiogenic tyrosine kinase inhibitors currently in development for the treatment of non-small cell lung cancer.
authors.affiliation: University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27599-7305, USA. socinski@med.unc.edu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology; D002986:Clinical Trials as Topic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D047428:Protein Kinase Inhibitors; D020794:Receptor Protein-Tyrosine Kinases