TNF-alpha antagonist stops inflammation-induced colon cancer in its tracks

Individuals with the inflammatory bowel disease ulcerative colitis are at increased risk of developing colon cancer. New data generated by Naofumi Mukaida and colleagues at Kanazawa University, Japan, identified a central role for the soluble factor TNF-alpha in the development of colon cancer in mice in which inflammation of the bowel was induced by administration of azoxymethane (AOM) followed by repeated dextran sulfate sodium (DSS) ingestion. Expression of TNF-alpha was increased in the colon of normal mice treated with AOM and DSS and this was followed by the development of tumors in the colon. Mice lacking one of the receptors for TNF-alpha and mice treated with an antagonist of TNF-alpha were markedly protected from the effects of treatment with AOM and DSS, developing less inflammation of the colon and fewer tumors in the colon. As suggested by the authors, and by Ezra Burstein and Eric R. Fearon in an accompanying commentary, these data provide clear rationale for the idea that drugs antagonizing TNF-alpha (such as those used to treat individuals with rheumatoid arthritis) might be useful in reducing the risk of colon cancer in individuals with ulcerative colitis.

TITLE: Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis

AUTHOR CONTACT:
Naofumi Mukaida
Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
Phone: 81-76-265-2767; Fax: 81-76-234-4520; E-mail: naofumim@kenroku.kanazawa-u.ac.jp.

View the PDF of this article at: https://www.the-jci.org/article.php?id=32453

ACCOMPANYING COMMENTARY TITLE: Colitis and cancer: a tale of inflammatory cells and their cytokines

AUTHOR CONTACT:
Eric R. Fearon
University of Michigan Medical School, Ann Arbor, Michigan, USA.
Phone: (734) 764-1549; Fax: (734) 647-7950; E-mail: fearon@umich.edu.

Ezra Burstein
University of Michigan Medical School, Ann Arbor, Michigan, USA.
Phone: (734) 615-1172; Fax: (734) 647-7950; E-mail: ezrab@umich.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=34831