Chronic inflammation and colorectal cancer: the role of vascular endothelial growth factor

Colorectal cancer (CRC) is the third most frequently diagnosed cancer in males and the second in females worldwide. Accumulating evidence has demonstrated that patients with chronic inflammation in bowels have an increased risk to develop CRC. Various inflammatory cells and mediators produced during chronic inflammation are orchestrated through different molecular signaling pathways and lead to the formation of a microenvironment in favor of tumorigenesis. Vascular endothelial growth factor (VEGF), which can be induced by chronic inflammation, plays a pivotal role in tumor angiogenesis as well as tumor growth and metastasis. Antiangiogenic therapy targeting VEGF and its signaling pathways represents a promising strategy to inhibit colorectal tumorigenesis. Indeed, anti-angiogenic agents modulating VEGF ligands and their receptors have already exhibited great potential in treating patients with CRC, especially when combined with conventional chemotherapeutic agents. This review discusses the promoting role of chronic inflammation in colorectal tumorigenesis at different stages including tumor initiation, promotion, progression and metastasis, highlighting the contributory role of VEGF in angiogenesis during the development from chronic inflammation to CRC. It also describes the clinical significance of anti- VEGF therapy in the treatment of such disease.