Drugs being developed to fight obesity and clogged arteries may raise the risk of colon cancer, U.S. researchers warned.

Tests on mice showed the compounds, known as PPAR-delta agonists, can cause mice to grow pre-cancerous polyps.

The tests were done on mice bred to develop colon cancer and so do not necessarily apply to humans, but the team at Vanderbilt University in Nashville said the study suggested that companies testing these drugs might need to do more experiments before proceeding in people.

Dr. Raymond DuBois and colleagues worked with a copy of GlaxoSmithKline's experimental compound, known as GW501516.

It is being studied as a possible drug to improve cholesterol levels and perhaps reverse heart disease caused by metabolic syndrome -- the so called "syndrome x" marked by a tendency to abdominal fat, high blood pressure and poor cholesterol levels.

The drugs affect a protein called peroxisome proliferator-activated receptor-delta -- PPAR-d for short. This chemical doorway into cells is important in a number of biological functions, including metabolizing fats and some of the processes that underlie the clogging of arteries.

"We have shown that in over 80 percent of human colon cancers, this receptor was increased pretty significantly," DuBois, a cancer researcher, said in a telephone interview.

"We wanted to pursue this to see if, in an animal that is susceptible to develop colon cancer, if the drug had any effect there."

Writing in the March issue of the journal Nature Medicine, DuBois and colleagues said they gave the drug to specially bred mice that spontaneously develop the little polyps that can lead to colon cancer.

The mice that got the drugs grew twice the usual number of polyps, and they were larger than usual.

"They had a pretty big effect," DuBois said.

This could mean that patients who already have polyps -- which do not cause any symptoms -- may be at higher risk of colon cancer if they take the drugs, the researchers warned.

DuBois, who had no communication with Glaxo and who actually obtained a synthetic copy of the drug, noted that big drug companies routinely test for cancer-causing effects. "But they usually don't test in these kind of animal models," he said.

"It's only a mouse study and we've seen these mouse studies before that didn't really apply to humans," he added.

"But these mice have the same mutations that humans (prone to colon cancer) get. So I think it is something that we need to be aware of and look out for."

Not only that, but the PPAR-delta receptor may be a target for drugs to battle colon cancer, he said. A drug that worked the other way, inhibiting the receptor rather than stimulating it, might treat the deadly cancer, DuBois said.

"We are definitely looking into that," DuBois said.

Colon cancer is the second-leading cause of cancer death in the United States after lung cancer, affecting nearly 150,000 this year and killing 57,000, according to the American Cancer Society.

Heart disease is the no. 1 cause of death and stroke, caused by factors including obesity. Clogged arteries ranks as the No. 3 cause of death after cancer.

A Glaxo spokesman said his company could not comment on the report but was studying it. He said the drug, which is in Phase II safety and efficacy trials in human volunteers, had been thoroughly tested by the company in the lab and no colon cancer effect had been observed.

Reference Source 89

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