VEGF-targeted therapy: mechanisms of anti-tumour activity

Vascular endothelial growth factor (VEGF) mediates numerous changes within the tumour vasculature, including endothelial cell proliferation, migration, invasion, survival, chemotaxis of bone marrow-derived progenitor cells, vascular permeability and vasodilation.There are several approaches to inhibiting VEGF signalling, including neutralization of the ligand or receptor by antibodies, and blocking VEGF receptor (VEGFR) activation and signalling with tyrosine kinase inhibitors.VEGF-targeted therapy has been shown to be efficacious as a single agent in renal cell carcinoma and hepatocellular carcinoma, whereas it is only of benefit when combined with chemotherapy for patients with metastatic colorectal, non-small-cell lung and metastatic breast cancer.VEGF-targeted therapy affects numerous cell types within the tumour microenvironment, including endothelial cells, haematopoietic progenitor cells, dendritic cells and tumour cells.VEGF-targeted therapy has multiple mechanisms of action that might be dependent on tumour type.VEGF-targeted therapy affects vascular function (flow and permeability) in addition to blocking further new blood vessel growth.