The Significance of The Renin Angiotensin System in the Screening, Diagnosis, and Treatment of Colorectal Cancer (CRC)

Nova Southeastern University, Davie, Florida, USA

Objective: The purpose of this study is to evaluate the possible use of angiotensin receptor biomarkers and angiotensin receptor blocker medications (ARBs) in the diagnosis and treatment of certain colorectal cancers (CRC) Background: Colorectal cancer (CRC) remains the third most common cause of cancer death in the United States. Multiple studies have demonstrated the overexpression of the A-II type 1 receptor (ATR1), which has been overexpressed in several human cancers. Methods: Methods as described in Goldstein et al.4 Results: In this analysis, we observed statistically significant alterations in many RAS related components gene expression in colorectal cancer specimens. AT1 receptor gene expression was unchanged. There was a highly significant reduction in Mas1 gene expression. There was a substantial increase in neprilysin gene expression in colorectal tumor tissue. Of note, Neprilysin is inhibited by sacubitril a component of the heart failure drug, Entresto® (sacubitril/ valsartan). It will be of interest to determine if patients on Entresto® have a reduction in colorectal cancer incidence. Conclusion: This analysis is consistent with involvement of the RAS in colorectal cancer. However, the pathological significance of the changes in RAS related gene expression will require continued assessment of the effects of drugs that inhibit or enhance the activities of these various RAS related components on the incidence and the survivability of colorectal cancer.