Multitargeted anti-angiogenic agents and NSCLC: clinical update and future directions.

Increasing understanding of the molecular abnormalities driving cell growth and proliferation has resulted in extensive research into molecularly targeted therapies. Angiogenesis is an appealing target for the treatment of non small cell lung cancer (NSCLC). Bevacizumab, a monoclonal antibody against circulating vascular endothelial growth factor (VEGF), is already approved for the treatment of NSCLC. Many other anti-angiogenic agents under development form the focus of this review. A variety of agents, including sorafenib, sunitinib, cediranib, axitinib, motesanib, linifinib and brivanib inhibit VEGF in addition to either platelet derived growth factor (PDGF), or fibroblast derived growth factor (FGF). To date, none of these agents in combination with chemotherapy have resulted in improvements in overall survival for patients with advanced NSCLC. Triple angiokinase inhibitors, which inhibit VEGF, PDGF and FGF, have potential to improve the therapeutic outcomes for patients with NSCLC. However, there is a need for identification of appropriate biomarkers to improve patient selection and identify those patients benefiting from anti-angiogenesis therapy.