Antiangiogenic drugs in non-small cell lung cancer treatment

Abstract

A promising therapeutic target is the vascular endothelial growth factor pathway - a key mediator of tumor angiogenesis - which is important in tumor growth, invasion, and metastasis. This review focuses on the available clinical data on drugs targeting the vascular endothelial growth factor - vascular endothelial growth factor receptor pathway in the treatment of non-small cell lung cancer. The therapeutic value of inhibiting the vascular endothelial growth factor pathway has been demonstrated by using drugs that prevent vascular endothelial growth factor receptor binding and by using drugs that inhibit receptor activation. Two antiangiogenic drugs exemplify these mechanisms: bevacizumab (Avastin; Genentech, South San Francisco, California, USA), a humanized monoclonal antibody that acts by binding and neutralizing vascular endothelial growth factor; and ZD6474 (Zactima; AstraZeneca, Macclesfield, UK), a small-molecule inhibitor of vascular growth factor receptor and epidermal growth factor receptor tyrosine kinase activity. Recently, the first results of a large, phase III randomized clinical trial of bevacizumab in combination with platinum-based doublet chemotherapy have been reported in patients with nonsquamous non-small cell lung cancer. The inhibition of tumor angiogenesis is a key therapeutic strategy that holds great promise for the advancement of metastatic lung cancer therapy. The combination of bevacizumab and conventional chemotherapy could offer a new therapeutic option in selected non-small cell lung cancer histotypes.