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Promise and Progress - Micromanaging Colon Cancer

Promise & Progress: Special Issue Bloomberg - Kimmel Institute for Cancer Immunotherapy
Issue No. 2016

Micromanaging Colon Cancer

Date: March 23, 2016

There is a microscopic society living within us.  Our bodies are home to more than 100 trillion microorganisms, more than 10 times the number of human cells in the body. Many of them reside in our gut. Most of the time, this microsociety—which includes hundreds of species of bacteria—and its human host coexist harmoniously.  The “bugs” we live with aid in digestion, metabolism and immunity.  

With such an overwhelming numbers advantage, it may only take the activity of a single organism to shift this harmonious relationship in a way that can promote cancer, says infectious disease expert Cynthia Sears

Of the trillions of possibilities, Sears has zeroed in on a population that appears to be related to colon cancer development.

The entire colon is lined with a thick protective layer of mucus, and, under normal conditions, bacteria are excluded.  In some colon cancers, however, Sears, researcher Christine Dejea, and team have found biofilms made up of a subset of bacteria that has managed to invade the mucus. “They invade the layer of mucus that protects the epithelial cells lining the colon and upend the whole biology of the system,” says Sears.

With so many different forms of bacteria colonized within the human body, it is a difficult task differentiating those that keep us healthy from those that contribute to disease. In this case, the association seems clear.  The risk of colon cancer may be as much as five times greater in patients who have biofilms in their colons compared to those who have none.                                                                                          

Sears doesn’t yet know how these biofilms develop, but she has a hunch about their link to cancer. She speculates that they cause inflammation in the colon, which spurs genetic mutations that lead to cancer. “When we look at people who undergo screening colonoscopy, we find a subset of people who have biofilms. What happens in that tissue and cells right under the biofilm, are the same processes we see in cancer.” Another mystery was related to the location of the biofilms. In her team’s study of 178 surgery or colonoscopy patients treated at either The Johns Hopkins or the University of Malaya Medical Centre in Malaysia, the vast majority of biofilms were located in the right colon. “It’s virtually a universal feature of tumors that appear in that section of the colon, although we don’t understand why,” says Sears.

To help answer some of these questions, Sears is working with cancer prevention and control expert Elizabeth Platz, cancer immunology expert Drew Pardoll, and gastroenterologist Francis Giardiello to a establish a large colonoscopy multicenter study to define the natural history of biofilms and their association to changes in tissue. “When we detect biofilms, where are they?  How long do they last, and what do they do? This is what we want to figure out,” says Sears.

The study will also establish a large bank of biofilm samples to integrate complex microbial and immune analyses. “ We want to understand how the immune system responds to biofilms as well as the gene expression of these bacterial communities and how they interact with other bacteria inside of the biofilm,” she says.

Biofilms are a new discovery, and Sears and team are the first to systematically explore them in colon cancer.

Patients with an inherited form of colon cancer, known as familial adenomatous polyposis (FAP) may provide some early answers. The disease is characterized by large numbers of polyps in the colon. Sears says FAP sufferers also develop many biofilms, but instead of being made up of many types of microorganisms, they primarily consist of two types of bacteria. “This is the best evidence so far that particular organisms may be relevant, and it may help us zero in on the bacteria that could be pushing this process,” says Sears.

Among her long-term goals, Sears hopes to use her findings to develop a noninvasive test to detect biofilms and predict a person’s risk of developing cancer. “Most colon cancers are known to develop slowly over time,” she say.  “It’s a disease that’s curable if diagnosed early, and maybe biofilms are an early warning sign.”