Chemotherapy and antiangiogenic agents in non-small-cell lung cancer

Angiogenesis, the growth of new vessels from preexisting vessels, is a fundamental step in tumor growth and progression. Tumor-related angiogenesis has become an attractive target for anticancer therapy. Vascular endothelial growth factor (VEGF) is a key angiogenic factor implicated in tumor blood vessel formation and permeability. Overexpression of VEGF has been observed in a variety of cancers and has been associated with a worse relapse-free and overall survival. A large randomized trial recently demonstrated an improvement in overall survival when bevacizumab, a humanized monoclonal antibody against VEGF, was combined with chemotherapy in patients with advanced non-small-cell lung cancer. Small molecule inhibitors targeting the VEGF receptor and the tyrosine kinase receptor have also shown promise when combined with standard chemotherapeutic agents in patients with advanced non-small-cell lung cancer. There is emerging evidence that inhibition of a single target leads to upregulation of other angiogenic signaling cascades. Future directions will include the use of these agents in combination with one another as well as in combination with chemotherapy and radiation therapy in patients with early-stage (IA-IIIB) disease.