Bevacizumab is a
monoclonal antibody that binds and neutralizes
vascular endothelial growth factor (
VEGF)-A, a key player in the angiogenesis pathway. Despite benefits of
bevacizumab in
cancer therapy, it is clear that the
VEGF pathway is complex, involving multiple
isoforms, receptors, and alternative
ligands such as
VEGF-B, and placental
growth factor, which could enable escape from
VEGF-A-targeted angiogenesis inhibition. Recently developed
therapies have targeted other
ligands in the
VEGF pathway (eg,
aflibercept, known as
ziv-aflibercept in the United States),
VEGF receptors (eg,
ramucirumab), and their
tyrosine kinase signaling (ie,
tyrosine kinase inhibitors). The goal of the current review was to identify comparative preclinical data for the currently available
VEGF-targeted
therapies. Sources were compiled using PubMed searches (2007 to 2012), using search terms including, but not limited to: "
bevacizumab," "
aflibercept," "
ramucirumab," and "IMC-18F1." Two preclinical studies were identified that compared
bevacizumab and the newer agent,
aflibercept. These studies identified some important differences in binding and pharmacodynamic activity, although the potential clinical relevance of these findings is not known. Newer antiangiogenesis
therapies should help further expand treatment options for colorectal and other
cancers. Comparative preclinical data on these agents is currently lacking.