Angiogenesis Inhibitors and Their Therapeutic Potentials

Abstract

The observation that tumor growth is accompanied by increased vascularity was reported nearly a century ago’. The therapeutic potentials that target tumor blood vessels was suggested more than three decades ago’. Inspired by this hypothesis, many investigators have jointed to the field of antiangiogenesis with an obvious goal of finding angiogenesis inhibitors that block tumor growth and metastasis. Over the last decade, the field of antiangiogenesis has become one of the key focuses in development of new cancer therapeutic drugs. The simple reason that angiogenesis research has received tremendous surge is that other anti-cancer therapeutic strategies including chemotherapy and radiotherapy do not seem to effectively block tumor growth. On contrary, they often produce toxic side-effects and therapeutic resistance. Thus, the antiangiogenesis approach has raised a new hope for cancer patients.Less than 10 years ago, only a few compounds, including several small chemical molecules and a couple of endogenous protein molecules have been described as angiogenesis inhibitors. These few angiogenesis inhibitors were barely enough to make a publishable table in a review article. Today, discovery of novel angiogenesis inhibitors has become a competitive business among many pharmaceutical companies with a hope to commercialize these compounds as therapeutic drugs against cancer and other angiogenesis dependent diseases. As a result, there is almost a new angiogenesis inhibitor being identified or reported every other week. Thus, it is almost impossible to give a complete overview of the entire field. According to their actions, angiogenesis inhibitors can be classified as: 1) Angiogenic factor antagonists; 2) Angiogenic factor receptor antagonists; 3) Protease inhibitors; 3) Anti-inflammatory compounds; 4) Matrix protein antagonists; 5) Cytokines; and 6) Direct endothelial cell inhibitors. Preclinical studies show that most of angiogenesis inhibitors effectively block tumor growth