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
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.