Control of colorectal cancer needs to be tailored to its etiology. Unlike sporadic or inherited tumors, colitis–associated colon tumors do not require cyclooxygenase (COX) activity for progression, and non-steroidal anti-inflammatory drugs (NSAIDs) which prevent sporadic or inherited colon cancer do not prevent colitis-associated colon cancer. Myeloperoxidase (MPOx), an ancestor of the COX isoenzymes, is a determinant of colitis-associated colon tumors in ApcMin/+ mice. During experimentally induced colitis, inhibition of MPOx dampens colon tumor development. Acrolein, a by-product of MPOx catalysis, forms a covalent adduct with the phosphatase tensin homolog (PTEN) tumor suppressor and enhances the activity of the Akt kinase proto-oncogene in vitro and in vivo. Thus, MPOx may be an important determinant of diet and inflammation on colon cancer risk via its effect on endogenous exposure to oxidants and acrolein.
The same MPOx by products above have been found in the bowels of inflammatory bowel disease patients. They may be an important determinant of increased colorectal cancer risk in these patients. Especially as several studies have shown a severity correlation of colitis associated colorectal cancer with MPOx activity.
Additionally, stem cell therapy in inflammatory bowel disease models has shown, among other effects, a reduction in MPOx activity.
We are currently in the process of setting up a clinical trial targeting MPOx activity chemically or using stem cell therapy in IBD patients.