Combined targeted therapies in non-small cell lung cancer: a winner strategy?

Abstract

Current treatment modalities provide limited improvement in the natural course of lung cancer, and prognosis remains poor. Lung cancer is a malignancy with great molecular heterogeneity. The complexity of the signalling process leading to cancer cell proliferation and to the neoplastic phenotype supports the necessity of interfering at different stages to avoid cancer cell resistance to therapy. Use of several agents with multiple growth factor receptor or intracellular targets has shown encouraging results in phase I and II clinical trials in non-small cell lung cancer. ZD6474 is a dual epidermal growth factor receptor and vascular endothelial growth factor receptor 2 small-molecule tyrosine kinase inhibitor; sorafenib is an oral kinase inhibitor of Raf-1 and is also active against vascular endothelial growth factor receptors 2 and 3, platelet-derived growth factor receptor beta, and c-KIT. Sunitinib is a vascular endothelial growth factor receptor 1, 2, and 3, c-KIT, and platelet-derived growth factor receptor alpha and beta tyrosine kinase inhibitor. Combined use of epidermal growth factor receptor-tyrosine kinase inhibitor erlotinib and the humanized vascular endothelial growth factor receptor monoclonal antibody bevacizumab in advanced, chemotherapy-refractory non-small cell lung cancer has shown promising results.