Tumor vasculature as a therapeutic target in non-small cell lung cancer

We aim to describe the molecular mechanisms relevant to angiogenesis inhibition and to critically evaluate the current evidence for the use of angiogenic inhibitors (AIs) in the treatment of non-small cell lung cancer (NSCLC). Methods: The literature on the basic concepts of tumor angiogenesis is reviewed. Published articles and major lung cancer conference abstracts were screened for reports on the use of AI in NSCLC patients and the National Institutes of Health clinical trials database was searched for relevant ongoing studies. Results: We delineate in this review the molecular and cellular aspects of angiogenesis and vasculogenesis and outline the relevance of these to lung cancer. Clinical studies of AIs in NSCLC reported to date as well ongoing studies are summarized. Major issues discussed include the choice of the right molecular target; characteristics of various tyrosine kinase inhibitors; potential drawbacks and concerns regarding the application of AIs in clinical practice, and major unanswered questions and future directions. Conclusions: AIs have antitumor activity in NSCLC and have become part of the standard of care for patients with advanced nonsquamous cell carcinoma. Unfortunately, the gains have been modest and robust predictive biomarkers are urgently needed. Clinical trials to date have validated the tumor vasculature as a legitimate target, and as our understanding of the biology of tumor angiogenesis increases, exciting new therapeutic approaches are being explored.