Modes of Neovascularization in Tumors and Clinical Translation of Antiangiogenic Therapy

Blood vessels deliver oxygen and nutrients to every part of the body, but also nourish diseases such as cancer. Recently, our understanding of the molecular mechanisms of angiogenesis has increased at an explosive rate and has led to the approval of antiangiogenic drugs for cancer and eye diseases. So far, hundreds of thousands of patients have benefited from blockers of the angiogenic protein vascular endothelial growth factor, but limited efficacy and resistance remain outstanding problems. Recent studies have shown new molecular targets and principles, which may provide avenues for improving the therapeutic benefit from antiangiogenic strategies. Our group and others have demonstrated that the blood and lymphatic vasculature, fibroblasts, immune cells, and the extracellular matrix associated with tumors are abnormal, and together create a hostile tumor microenvironment. Antiangiogenic agents – originally designed to starve tumors – can transiently ‘normalize’ tumor vasculature, alleviate hypoxia, and improve the outcome of various therapies.