Anti-angiogenic therapy in breast cancer
Molecular effects induced by angiogenic inhibitors
Angiogenesis (stimulation of new blood vessel formation) is a normal process in growth and development, as well as in wound healing. However, it is also a fundamental step in the transition of tumours from a dormant state to a malignant state. VEGF (Vascular endothelial growth factor) is a protein that is secreted by oxygen-deprived cells, including malignant cells, and stimulates new blood vessel formation by binding to receptors on nearby blood vessels.
Bevacizumab is a humanized monoclonal antibody against VEGF and was the first commercially available angiogenesis inhibitor. It stops tumor growth by preventing the formation of new blood vessels by targeting and inhibiting the function of VEGF. However, even though the effect of bevacizumab is well documented, its molecular effects in breast cancer are not well explored. In particular, studies revealing the molecular effects of bevacizumab in combination with endocrine therapy and chemotherapy are lacking. Therefore, we will investigate the level of phosphorylated VEGF in human breast cancer xenografts after anti-angiogenesis therapy and chemotherapy, either separately or in combination. The results from these experiments will give indications of signalling pathways that are activated in the different xenografts representing two different subgroups of breast cancer upon treatment, which can further be translated into future personalized therapy. For more information contact Evita Lindholm.