After my aunt died from colorectal cancer several years ago, my father was primed when his doctor suggested he get screened for colon cancer himself, and it’s a good thing he did. The doctor who performed the colonoscopy (a visual exam of the rectum and colon) found a large precancerous polyp.
If my father had skipped out on being screened, he would likely have been dead in five years. He was lucky that the polyp was easily visible during the exam, but not all lesions that turn out to be cancerous are. Some pre-cancerous areas are flat or depressed and much harder to see on colonoscopies or sigmoidoscopies.
Now, a team of Stanford researchers led by Matthew Bogyo, PhD, a professor of pathology and microbiology and immunology, are working on ways to make these less obviously cancerous regions on the colon more visible during screenings. They're doing so by developing compounds that begin to fluoresce - or glow - when they attach themselves to enzymes called cysteine cathepsins. Present in nearly all cells of our bodies, cysteine cathepsins are abundant in and around cancerous tumor sites. “They’re regulators of inflammation,” Bogyo said when we spoke recently. “When a tumor starts to form, you get inflammation, and the tumor benefits from this inflammatory response. We take advantage of that inflammation, using these enzymes as markers.”
The researchers studied how well the compounds, called quenched fluorescent probes, identified lesions in two strains of mice - one, a specially bred strain of mice that produce a higher number of intestinal polyps and the other a wild-type mouse in which colon cancer is induced by a orally administered drug - as well as in human tissue samples. Their study was published today in the scientific journal Chemistry and Biology. A statistical analysis of the results showed that the probe was highly effective at identifying true cases of intestinal lesions and had a low rate of false positives. “Optical contrast agents allow us to see where lesions are and pick out problem areas,” Bogyo told me. “When they are 'found' by these enzymes, they turn bright.” Although it's hard to compare a test like this to current methods of colorectal cancer screening, which do not involve the use of contrast agents, Bogyo is encouraged by the study’s results.
Bogyo noted that he was surprised that the probe worked just as well identifying lesions in mice intestines when it was applied topically to the inside surface of the intestines as when it was injected into the bloodstream. This opens up the possibility that - if approved for use in humans - it could simplify how the probe is used. A colonoscopist could simply spray the contrast agent out of the end of the endoscope to get a confirmation of potentially dangerous lesions.
Getting these kinds of probes into human use is still years away. Currently, no other targeted optical contrast agents are approved for human use, and the process of gaining approval from the Federal Drug Administration, much like developing a new drug, can be an expensive and arduous one. The probes would need to be tested for safety in animals and eventually humans before they could be approved for widespread use.
But the field is a promising one, and Bogyo is not the only researcher pursuing contrast agents as cancer-screening tools. He is optimistic and is currently exploring companies that may want to invest in developing cysteine cathepsin contrast agents for human use. Incorporating contrast agents into current practices “would move the field forward and make colonoscopy more accurate and rapid,” he said.
Previously: Researchers explore colonoscopy's effect on the incidence of colorectal cancer, No day on the beach: A colon cancer survivor's story, The cost-effectiveness of screening colon-cancer patients for Lynch disorder and Bacterial balance in gut tied to colon cancer risk
Photo of colon cancer cells by Wellcome Images