Investigating the use of 5-aminosalicylic acid for chemoprophylaxis

in individuals at increased risk of developing colorectal cancer

Summary

Most colorectal cancers (CRC) arise sporadically from precursor lesions: colonic polyps. Removing colonic polyps prevents progression to CRC. Risk of future polyps is proportional to the number and size of polyps detected at screening, allowing identification of high-risk individuals. Despite further surveillance, nothing is offered to reduce the risk of developing new polyps for these patients.
Our recent findings have shown that low doses of mesalazine, (5-ASA) a medication used in the treatment of ulcerative colitis, can inhibit the growth of human polyp cells in 3-dimensional models of colorectal tumorigenesis. Mesalazine is an affordable and well-tolerated drug with decades of clinical experience in the treatment of ulcerative colitis which makes it an excellent candidate for repurposing as a cancer preventative agent. To enable future clinical trials, the aim of this study is to identify a panel of mechanistic markers that will indicate whether mesalazine is having an effect (so that we are not solely reliant on polyp number) and address the dose required for polyp prevention. The purpose is to gather data to support an application to fund a clinical study to determine the benefit of regular 5-ASA treatment for the prevention of sporadic colorectal cancer.
Given the increasing number of younger people being diagnosed with CRC, it is hoped that prescribing mesalazine to high-risk individuals will not only reduce the occurrence of cancer but also reduce the need for repeat colonoscopy, so that limited screening capacity currently available could be used to include younger individuals.