New Treatment Could Prevent Leading Cause of Death in Hereditary Colon Cancer Survivors

Those born with the inherited genetic condition, familial adenomatous polyposis (FAP), have a nearly 100 percent lifetime risk for colon cancer. Let that sink in for a moment - they WILL get cancer if they do not take action. Many patients opt for the most aggressive prevention: they have their colon surgically removed.

For 15 percent of patients even that is not enough. They still develop cancer in the small intestine, an organ that can’t be removed. Instead, doctors keep cancer at bay by cutting out precancerous polyps before they bloom into disease. But carrying out surgery in the narrow, winding organ is a tricky prospect, making it difficult to remove polyps completely. As a result, cancer of the duodenum, the upper intestine, is the leading cause of death in FAP patients.

A clinical trial led by Huntsman Cancer Institute investigators, and published in JAMA, has found a drug treatment that provides precision prevention for this group of high-risk patients. A combination of two drugs, sulindac (COX-2 inhibitor) and erlotnib (EGFR inhibitor), reduces precancerous polyps in the small intestine by 75 percent.

Deb Neklason“It was a huge response. The doctors said they had never seen anything like it for small bowel cancers,” says co-author Deborah Neklason, Ph.D., Huntsman Cancer Institute investigator and program director of the Utah Genome Project. She says the novel drug therapy has great promise. “We are working hard to establish a drug treatment for driving away precancerous polyps. That will be a great success.”

The latest discovery is a significant milestone in care for patients who need it most. As recently as 35 years ago, no one even knew FAP existed, let alone how to treat it. The first hint came when members of a Utah family approached University of Utah physicians. They had a distressing pattern of colon cancer and early deaths throughout their family tree, but no one knew why.

With the help of family members, scientists researched their illness, mining the Utah Population Database - the world’s large resource of medical, population, and genealogical data - for its cause. They found that a mutation in the gene adenomatous polyposis coli (APC) snaked through their tree, bringing colon cancer not only to family they knew but also to distant relatives throughout the country and the world.

Years later, follow-up studies in animal models revealed the molecular pathways through which the disease gene drives cancer. These results informed the one-two punch tested in the new clinical trial. An existing drug, erlotnib, blocks the errantly activated pathway, and was given in combination with the anti-inflammatory drug sulindac, known to suppress polyp growt

Though FAP is rare, these discoveries could have implications for treating sporadic colon cancer, one of the most common cancers in the U.S. APC, the disease gene that causes the inherited condition, is also mutated in 80 percent of colon cancers.

“There is some really exciting analogies with sporadic colon cancer,” says Neklason. “It’s quite possible that some of this new knowledge can be applied toward prevention and potentially even treatment the disease, which impacts hundreds of thousands across the country.”

See also:

New Treatment Reduces Precancerous Polyps in Hereditary Cancer Patients

Listen to an interview about the research on The Scope Radio



Advancing care for those at highest risk