New angiogenic agents and non-small cell lung cancer: current results and future development

New blood vessel formation, known as angiogenesis, is a fundamental event in the process of tumor growth and metastatic dissemination. Due to its central role in tumor angiogenesis, the vascular endothelial growth factor (VEGF) and its receptor have been a major focus of basic research and drug development in the field of oncology, including the treatment of non-small cell lung cancer (NSCLC). Approaches targeting VEGF include monoclonal antibodies and vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs). To date, bevacizumab, an anti-VEGF recombinant humanized monoclonal antibody, is the first targeted agent that, when combined with chemotherapy, reported superior efficacy versus chemotherapy alone in the treatment of advanced NSCLC. Several angiogenetic agents are being evaluated in clinical research and some of them, such as ZD6474, sorafenib and sunitinib, seem to be promising targeted agents for the treatment of NSCLC because of evidence of antitumor activity, an excellent toxicity profile and oral administration. The complexity of the signaling process leading to cancer cell proliferation and to the acquisition of a neoplastic phenotype supports the necessity to interfere at different stages to avoid an escape of potential resistance mechanisms. Targeting multiple pathways in tumor cells should be an effective strategy of treatment in NSCLC. Clinical trials of multiple targeted therapy may represent the second generation of studies in this setting.