Abstract
As tumors grow and metastasize, they require the formation of new blood vessels or angiogenesis. This process is regulated by a complex balance of pro- and antiangiogenic factors. One of these factors, vascular endothelial growth factor (VEGF), has been extensively studied and found to be an important stimulatory signal. that drives angiogenesis. VEGF belongs to a family that consists of six glycoproteins and binds to one or more of the three VEGF receptors. The various VEGF ligands and receptors mediate angiogenesis, vasculogenesis, and lymphangiogenesis. Recently, neuropilins have been shown to be important co-receptors and help to modulate VEGF and VEGF receptor interactions. VEGF and its receptor have become targets for monoclonal antibody therapies in the treatment of various cancers. Bevacizumab, which is directed against VEGF, has been the most extensively studied drug with several phase III trials already completed. Based on improvement in patient survival, bevacizumab has been FDA approved for use in combination with chemotherapy for the treatment of metastatic colorectal cancer, non-small cell lung cancer, and breast cancer. Although most of the trials investigating bevacizumab involved treating patients with advanced disease, there are two ongoing phase III trials of bevacizumab in combination with cytotoxic chemotherapy in the adjuvant setting in patients with advanced stage epithelial ovarian cancer. Newer antibody therapy directed at VEGF (VEGF-Trap and HuMV833) and VEGF receptor (IMCL- 1121b and IMC-18F1) is still in development and early clinical trials. Despite the improvements in patient survival, several challenges still lie ahead and include potential serious side effects such as gastrointestinal perforation, determining appropriate dosing, dealing with resistance to antiangiogenesis drugs, and identifying biologic markers for predicting and monitoring response to therapy. Targeting VEGF has been an important novel strategy in treating cancers and will continue to improve with our understanding of angiogenesis in malignancy.