VEGF inhibition and metastasis: Possible implications for antiangiogenic therapy

Abstract

Since the 2004 approval of bevacizumab, a humanized monoclonal antibody that

binds vascular endothelial growth factor (VEGF), antiangiogenic therapy has been used

to treat selected cancers, including colon, non-small cell lung, and breast cancers.  In

addition to bevacizumab, the FDA has approved two other antiangiogenic therapies;

sorafenib and sunitinib, both of which are tyrosine kinase inhibitors that target VEGF

receptors, particularly VEGFR2.  However, even with the approval of these three drugs,

antiangiogenic therapy has not yet had the impact some have hoped for. Many clinical

benefits are short-lived; while numerous trials have shown an increase in survival in

patients treated with antiangiogenic therapy, the increase for many was a matter of

months.1 While any improvement in overall survival should be regarded as an

accomplishment, it is important to understand why such clinical improvements are

sometimes fleeting so that newer therapies can result in more enduring benefits.