Molecular mechanism of angiogenesis in colorectal cancer

Colorectal cancer (CRC) is one of the healthcare burdens in South Africa with a high probability of cancer relapse. Colorectal cancer has been demonstrated to be caused by oncogene activation and deactivation of tumor suppressor genes in the system. Human diseases such as cancer have been reported to be associated with vascular dysfunction which contributes to malignancy, tumor evasion, and metastasis. Vascular dysfunction in most tumors has led to treatment resistance and cancer relapses. The expression of vascular endothelial growth factor is mediated by HIF-1 during oxidative stress, hypoxic conditions, or mediated by epidermal growth factor receptor as an oncogene in the development of new abnormal blood vessels in tumors, as well as metastasis in CRC. Angiogenic targeted therapies that are developed thus far against colorectal cancer have been shown to improve the survival rate of patients, nonetheless, poor prognosis is still a major issue for metastatic CRC. Angiogenesis is a critical and promising target for the inhibition of tumor growth, progression, and metastatic CRC therapies. In this review, we report some of the molecular mechanisms of angiogenesis in colorectal cancer. The roles of epidermal growth factor receptor (EGFR), Hypoxia-induced factor-1 (HIF-1), and miRNAs as factors that contribute to the induction of VEGF activity to elicit tumor angiogenic pathway in colorectal cancer. Despite the limitations of CRC therapies, several studies have shown that the combination of conventional therapies and pro-angiogenic agents has slightly improved the survival rate of patients. Moreover, studies have shown several ways to target the pro-angiogenic factors in combating tumor angiogenesis and more research is still required to understand the molecular mechanism and pathogenesis of CRC.