VEGF and angiogenesis: implications for breast cancer therapy

Angiogenesis is essential for tumour growth, progression and metastasis. Vascular endothelial growth factor (VEGF) is a key angiogenic mediator, and has been shown preclinically to play multiple roles in the development and maintenance of abnormal tumour vasculature, while playing a limited role in adults. VEGF is thus an attractive therapeutic target. Bevacizumab is a humanised anti-VEGF monoclonal antibody and has extensive effects on tumour vasculature as demonstrated by a number of preclinical studies. Its mechanism of action and preclinical evidence indicate that it regresses new tumour vasculature, normalises the dysfunctional and chaotic existing tumour vasculature, and prevents the formation of additional tumour vasculature. Although the drug target of bevacizumab is well known, no biomarkers have been identified that predict the clinical benefit from targeting circulating VEGF with bevacizumab. The mechanism of action of bevacizumab with regards to direct antitumour effects has not been elucidated. Future clinical studies will provide additional evidence for the effectiveness of bevacizumab in combination with a variety of different chemotherapy and biological agents.