Angiogenesis inhibitors in the treatment of non-small cell lung cancer.

A therapeutic plateau seems to have been reached with the standard treatment of cytotoxic chemotherapy alone for advanced stage non-small cell lung cancer (NSCLC) and new treatment options are urgently needed. Recent insight into the molecular biology of cancer has identified angiogenesis as one of the key biological processes. The major player in tumor angiogenesis is the vascular endothelial growth factor (VEGF) pathway. VEGF is expressed in the majority of NSCLC and overexpression is associated with a poor prognosis. The VEGF pathway can be inhibited in two main ways: targeting VEGF directly or inhibiting the VEGF receptors. The development of angiogenesis inhibitors has shown great promise in the treatment of NSCLC. Bevacizumab, an anti-VEGF antibody, has been approved for the treatment of advanced NSCLC and other drugs are undergoing phase III investigation. However, a number of unresolved issues remain. In this review, we discuss the main angiogenesis inhibitors in development for the treatment of NSCLC focusing on the VEGF pathway.