Angiogenesis, the physiological process of sprouting of new blood vessels from pre-existing ones, is a key biological feature of almost all
cancers. Among the multitude of factors driving
tumor angiogenesis,
vascular endothelial growth factor (
VEGF) is the most potent, exerting myriad effects on vascular pruning and sprouting, permeability, network formation, proliferation, and cell death. Despite the initial unimpressive clinical performance of anti-
VEGF antibody (
bevacizumab) as
cancer monotherapy, clear improvements in clinical outcomes following combination
bevacizumab and
chemotherapy regimens and multi-targeted
VEGF receptor tyrosine kinase inhibitors (
sorafenib and
sunitinib) in select
tumor types have established
VEGF-targeted agents as an effective means of controlling
cancer growth. Prolongation of overall survival and cure with these agents, however, remains elusive. Moreover, recent data has revealed key differences in the therapeutic and biological
tumor response to antibody versus receptor
kinase VEGF inhibitors and suggested, at least pre-clinically, that
VEGF blockade in certain circumstances may actually promote more aggressive
tumor growth. Given the diverse mechanisms and potentially opposing roles of
VEGF neutralization in
cancer biology, identification of novel
biomarkers predictive of in vivo angiogenic responses may hold the key to optimizing therapeutic outcomes of anti-
VEGF therapy in future
cancer patients.