Small Molecules Pack a Big Punch in Colon Cancer Prevention

By: Valerie Lauer
Tuesday, December 9, 2014

Promising research may lead to therapies that help prevent colitis-induced cases of colon cancer.

Researchers from Case Western Reserve University and Dartmouth Medical School tracked the effects of a small antioxidant molecule, CDDO-Me, on mice engineered to be susceptible to colon cancer.

A Case for Chemoprevention

The team examined the potential of CDDO-Me, a synthetic triterpenoid, as a chemopreventive agent — a substance that can stop cancer before it starts or interrupt or reverse the course of the condition.

Because colitis-induced colon cancer has been extensively researched and its mechanisms are at least partially understood, this serious yet common disease was an ideal fit for the research.

The team found a direct correlation between the application of CDDO-Me as an oral supplement and the suppression of colon cancer in mice with inflammatory bowel disease (IBD). The molecule also counteracted the 15-PGDH enzyme deficiency that makes some patients unresponsive to colon cancer treatment with COX-2 inhibitors, normally a highly effective therapy both for prevention and treatment of the disease.

“It’s very possible that exposure to a triterpenoid may either make [patients] more sensitive to COX-2 inhibitors or reduce the dose of COX-2 inhibitors they need to achieve clinical benefit,” says the study’s lead author, John Letterio, MD, Professor of Pediatrics at Case Western Reserve University School of Medicine and Director of the Angie Fowler Adolescent & Young Adult Cancer Institute, University Hospitals Rainbow Babies & Children’s Hospital.

Looking Ahead

The American Cancer Society estimates that more than 50,000 Americans will die from colon cancer in 2014. IBD is associated with a 10-times-greater risk of developing colon cancer. Triterpenoid therapy offers the potential to decrease the number of colitis-induced cases of colon cancer and improve treatment for existing patients.

“Death … from heart disease has plummeted in our lifetime, and it’s not because of faster ambulances or better defibrillators. It’s because we’ve developed drugs to lower cholesterol and to treat hypertension. The question is, can we develop similar strategies for the cancer problem and reduce the burden of the disease?”
— John Letterio, MD, Professor of Pediatrics at Case Western Reserve University School of Medicine, Director of the Angie Fowler Adolescent & Young Adult Cancer Institute, University Hospitals Rainbow Babies & Children’s Hospital

Research supports the use of triterpenoids in the treatment of many types of cancer, such as breast cancer, due to their anti-inflammatory properties and multifunctional abilities that researchers are just beginning to fully understand. In preclinical trials, triterpenoids have also been shown to prevent and reverse neurological damage associated with multiple sclerosis. At this time, the use of triterpenoids as a clinical chemopreventive therapy is not approved.

At Case Western Reserve, Dr. Letterio and his collaborators plan to continue their research into triterpenoid chemoprevention for colon cancer. They hope further research will help make the therapy a staple of cancer prevention.

A summary of the team’s findings appeared in the June 2014 issue of the Journal of Clinical Investigation.