Angiogenesis as a therapeutic target in advanced breast cancer
Therapy of metastatic breast cancer is still palliative with a very low probability to induce complete remission and definitive cure of disease. The relevant efforts of basic research to identify the key and selective molecular alterations, which sustain breast cancer growth and progression allowed developing specific molecular target treatments. Angiogenesis, the process of new blood vessel formation, is required for tumour growth and metastasis. There is substantial preclinical and clinical evidence supporting the central role of angiogenesis in tumour formation and metastasis. Thus, the inhibition of angiogenesis may provide an effective treatment for patients with advanced breast cancer. Several chemotherapeutic and hormonal agents routinely used in cancer treatment have antiangiogenic properties. Novel antiangiogenic agents targeting the vascular endothelial growth factor ligand and receptor tyrosine kinase inhibitors are being developed. Recently, a large phase III clinical trial demonstrated a significant benefit in progression-free survival with the addition of anti-VEGF monoclonal antibody bevacizumab to paclitaxel for first-line treatment of advanced breast cancer. This study established that antiangiogenic therapy is effective in advanced breast cancer, and additional studies of antiangiogenic agents are under way. This review provides an updated overview of the role of angiogenesis in breast cancer pathogenesis, the challenges of developing antiangiogenic agents, and current agents in clinical trials.