Multitargeted receptor tyrosine kinase inhibition: An antiangiogenic strategy in non-small cell lung cancer

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. (C) 2011 Elsevier Ltd. All rights reserved.