Angiogenesis and Oxidative Stress in Metastatic Tumor Progression: Pathogenesis and Novel Therapeutic Approach of Colon Cancer

Background: When tumor cells are under hypoxic condition or other forms of oxidative stress, one of the survival mechanisms is to undergo angiogenesis, involving dissemination of existing vessels or neovascularization to antagonize the apoptotic drive and to facilitate migration to secondary sites. Methods: This paper reveals the pathogenesis of tumor angiogenesis, particularly during hypoxia and other forms of oxidative stress in cancer cells. Results: Following successive invasion of the extracellular matrix (ECM), new blood vessels penetrate and supply nutrients to tumor tissues for growth and metastasis. The metastatic power of cancers is determined by a series of angiogenic and metastatic factors. These factors could allow neoplastic tissues to survive and withstand the stress induced by hypoxia and/or disruption of the ECM, including vascular endothelial growth factor and matrix metalloproteinases that were found to be highly elevated in tumor tissues of colon cancer patients. These aggressive factors could be regulated by cancer signaling pathways such as the phosphatidylinositol 3- kinase/Akt/mTOR cascade. In fact, mTOR (the mammalian target of rapamycin) acts as a central regulator of many cellular activities involving growth and differentiation through regulation of cell cycle progression, cell size, cell migration and survival, including those in tumor cells. Several novel therapeutic approaches that target the angiogenic drive of cancers have been introduced, including compounds derived from natural products and synthetic chemicals. Conclusion: This article highlights the importance of angiogenesis and oxidative stress on the development of advanced and metastatic colon cancers, and provides new insights on alternative and effective treatment options.