Targeting angiogenesis with multitargeted tyrosine kinase inhibitors in the treatment of non-small cell lung cancer.
It has been >35 years since the link between angiogenesis and the growth of tumors was first reported. Targeting angiogenesis became feasible with the availability of bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody. Initial studies revealed that the combination of bevacizumab and chemotherapy led to longer overall survival times than with chemotherapy alone in patients with advanced colorectal cancer. Since then, drug development strategies have added small molecule tyrosine kinase inhibitors to the panel of antiangiogenic agents under evaluation; data from numerous trials are now available. The challenge now is to identify the optimal antiangiogenic agent for specific patient groups and to understand not only the mechanistic differences between agents, but also the variability in their antitumor activity across different tumor types and their differing side-effect profiles. As in other solid tumors, angiogenesis contributes to the development of non-small cell lung cancer (NSCLC), and this review summarizes the role of angiogenesis in this disease. We review the current developmental status of antiangiogenic tyrosine kinase inhibitors (including vandetanib, sunitinib, axitinib, sorafenib, vatalanib, and pazopanib) in NSCLC and conclude by briefly discussing the need for optimal patient selection and potential future directions.
Scagliotti
Giorgio
G
University of Torino, Department of Clinical and Biological Sciences, S. Luigi Hospital, Orbassano (Turin), Italy 10043. giorgio.scagliotti@unito.it
Govindan
Ramaswamy
R
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D018579:Patient Selection; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases