Incorporation of Antiangiogenic Therapy Into the Non-Small-Cell Lung Cancer Paradigm

Although molecular targeted agents have improved the treatment of lung cancer, their use has largely been restricted to limited subsets of the overall population that carry specific mutations. Angiogenesis, the formation of new blood vessels from existing networks, is an attractive, more general process for the development of targeted anticancer therapies, because it is critical for the growth of solid tumors, including non-small-cell lung cancer. Growing tissues require a vascular supply within a few millimeters. Therefore, solid tumors create a proangiogenic microenvironment to facilitate the development of new tumor-associated blood vessels, thus providing an adequate vascular supply for continued tumor growth. Antiangiogenic agents can specifically target the vascular endothelial growth factor (VEGF) signaling pathways, broadly inhibit multiple tyrosine kinases, or interfere with other angiogenic processes, such as disruption of existing tumor vasculature. The present report provides an overview of antiangiogenic therapy for non-small-cell lung cancer, including both currently approved antiangiogenic therapies (bevacizumab [anti-VEGF] and ramucirumab [anti-VEGF receptor 2] monoclonal antibodies), and a variety of promising novel agents in development. Although recent data have demonstrated promising efficacy for some novel agents, the overall development of antiangiogenic therapy has been hampered by redundancy in signaling pathways and the highly heterogeneous nature of tumors. An improved understanding of the molecular basis of angiogenesis will guide the development of new antiangiogenic therapies and the identification of biomarkers to predict which patients with lung cancer are most likely to benefit from antiangiogenic therapy.