Angiogenesis is important in the growth and progression of solid tumours. The main pro-
angiogenic factor, namely
vascular endothelial growth factor (
VEGF), also known as
vascular permeability factor, is a potent angiogenic
cytokine that induces mitosis and also regulates the permeability of endothelial cells. The soluble
isoform of
VEGF is a dimeric
glycoprotein of 36-46 kDa, induced by
hypoxia and oncogenic mutation and it binds to two specific
tyrosine-kinase receptors: VEGF-1 (flt-1) and VEGF-2 (KDR/flk1). An increase in
VEGF expression in tumour tissue or some blood compartments (i.e. serum or plasma) has been found in solid and haematological
malignancies of various origins and is associated with
metastasis formation and poor prognosis.
Bevacizumab, a recombinant humanised
monoclonal antibody developed against
VEGF, binds to soluble
VEGF, preventing receptor binding and inhibiting endothelial cell proliferation and vessel formation. Pre-clinical and clinical studies have shown that
bevacizumab alone or in combination with a
cytotoxic agent decreases tumour growth and increases median survival time and time to tumour progression.
Bevacizumab is the first anti-angiogenetic treatment approved by the American Food and Drug Administration in the first-line treatment of metastatic
colorectal cancer. It has shown preliminary evidence of efficacy for breast, non-small-cell lung, pancreatic, prostate, head and neck and
renal cancer as well as haematological
malignancies. Common toxicities associated with
bevacizumab include
hypertension,
proteinuria,
bleeding episodes and thrombotic events. This review summarises the critical role of
VEGF and discusses the data available on
bevacizumab, from the humanisation of its parent murine
monoclonal antibody (mAb) A.4.6.1 to its use in
cancer clinical trials.