Targeting blood vessels for the treatment of non-small cell lung cancer.

Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Although modest survival benefit has been observed with surgery, radiotherapy and platinum-based chemotherapy, an efficacy plateau has been reached. It has become obvious, therefore, that additional treatments are needed in order to provide an improved survival benefit for these patients. The use of molecular targeted therapies, particularly those against tumor capillaries, has the potential to improve outcomes for NSCLC patients. Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), is the first targeted drug that has shown survival advantage when combined with chemotherapy in NSCLC. Other antivascular agents, including vascular disrupting agents (VDAs) and different small-molecule receptor tyrosine kinase inhibitors, have also shown promise in phase I and II trials in NSCLC. The aim of this study is to describe the clinical properties of these drugs and to discuss the evidence that supports their use in the treatment of NSCLC. Furthermore, we plan to review the main pitfalls of antivascular strategies in NSCLC cancer therapy as well as assess the future direction of these treatment methods with an emphasis on clarifying the molecular background of the effects of these drugs and defining the biomarkers.