New Hope for Patients with Familial Adenomatous Polyposis

Researchers at the University of California, San Diego, School of Medicine have discovered that common intestinal bacteria may promote tumor growth, but that introduction an inhibiting protein enzyme can prevent this promotion.

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Eyal Raz, MD, professor of medicine, UC San Diego, and his research team examined mice that were engineered with a mutation that closely mimics familial adenomatous polyposis (FAP), a disease that initially causes the formation of many benign polyps that later transform into malignant colon cancer. Mice with this engineered mutation were particularly vulnerable to inflammatory factors produced by ordinary bacterial activity, inflammation that enhances expression of the oncogene c-Myc. The mice quickly developed many tumors in their intestines and typically did not survive past six months.

Lead author

However, when the researchers gave the mice the protein enzyme extracellular signal-related kinase (ERK), it appeared to suppress intestinal turmorigenesis in the mice, causing rapid degradation of the cancer proteins and increasing the survival time of the mice.

“Our data reveal a new facet of oncogene-environment interaction, in which microflora-induced TLR activation regulates oncogene expression and related IEC tumor growth in a susceptible host,” the authors wrote in Nature Medicine

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"Right now, people with FAP don't have many options," said Raz. "They develop the cancer relatively early in life and the only treatment is surgery, often a total colectomy - the removal of the entire colon. And that still doesn't preclude the possibility of developing tumors elsewhere in the body. This [study’s results offer] a clear case of nature and nurture in molecular biology. Nature is the host, who in some cases is going to be genetically predisposed to develop certain diseases. Nurture is the environment, which in this case is bacterial activity and its effects. The mechanism for what's happening here with these mice and tumor growth is very clear. We know what we want and need to do."

Researchers at the University of California, San Diego, School of Medicine have discovered that common intestinal bacteria may promote tumor growth, but that this can be prevented when an inhibiting protein enzyme is introduced