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Research Target
Colorectal Cancer

Colorectal cancer is the second leading cause of cancer death in the United States, affecting an estimated 148,000 Americans each year and claiming more than 56,000 lives annually. In fact, 1 in 20 people will develop colon cancer at some time during their lives. Most colon cancer starts as a precancerous growth (polyp) that can be detected and removed during colonoscopy.

Detection Test Accurate, But Inconvenient & Expensive

It is well accepted that colorectal cancer is largerly preventable if caught at the polyp stage, and that the success rates for curing early colon cancer are much better than for advanced colon cancer. Colonoscopy, believed to be the most accurate test for detecting polyps and early colon cancer, is recommended for everone over age 50. However, it is inconvenient and expensive. Consequently, many people do not have this screening test done and do not follow any other screening recommendations to reduce the risk of colon cancer.

Develop Simple, Effective Screening Test

Researchers at UW Medicine and the Fred Hutchinson Cancer Research Center are trying to change this story. They are working on the development of a simple screening test for the disease that is equally as effective – but much more palatable to the public – than colonoscopy. An accurate new test that lacks the discomfort of colonoscopy is widely believed to have the chance to bump colorectal cancer from its rank as the second most deadly cancer in the United States.

Dr. William Grady’s lab is one such lab working to develop a safe, accurate and easy-to-administer test that picks up cancer warning signals in the DNA found in a blood or stool sample. Such a test would likely encourage more people to undergo screening. It would also limit the use of colonoscopy to those patients found to be at risk for cancer by the DNA test, who would then undergo the procedure to have polyps removed. Dr. Grady’s approach exemplifies the power of translational research. The goal of the research programs at UW Medicine and the Fred Hutchinson Cancer Research Center is to move discoveries of basic cancer biology out of the laboratory and into the doctor’s office.

With Early Detection, Chances of Survival Are About 95%

"The natural anatomy of the organs of the gastrointestinal (GI) tract, as well as the available technology for studying them, offer excellent possibilities for early cancer detection and cancer prevention – more so than for most other types of cancer," says Dr. Grady. This is because many cancers of the GI tract, particularly those in the colon or esophagus, tend to develop slowly. It takes about 10 years for a colon polyp to develop into cancer. With endoscopes – long, flexible tubes that can be equipped with cameras and forceps – doctors can acutally see inside the GI tract and remove suspicious growths. The DNA-based stool or blood test that Dr. Grady hopes to develop would identify individuals that have polyps that are likely to become cancerous well before they do. When colorectal cancer is caught in its earliest stage, chances for survival are about 95 percent.

Promising Molecular Markers for Targeting New Therapies

To create this new test, researchers, like Dr. Grady, in the UW GI Division are identifying the earliest molecular changes that can accompany a normal intestinal cell’s transition into cancer. Some of these changes involve chemical modifications to the DNA, called DNA methylation, and others involve mutations of the DNA. These molecular changes are not only promising molecular markers for colon polyps and cancer, but they are also targets for new therapies for colon cancer. Importantly, theses investigators must also develop strategies to overcome the technical obstacles in detecting minute amounts of cancer-related DNA in a vast sea of normal DNA located in the blood or stool. In order to do that, they have teamed up with researchers across the country, as well as with many of the local biotechnology companies, as a way to springboard these assays into clinical care.

Researchers at UW Medicine and at the Fred Huchinson Cancer Research Center are also studying how these molecular changes cause a normal cell in the colon to change into colon cancer. For instance, Dr. Grady’s lab also investigates the consequences that result when genes become methylated. The answers could lead to the development of new drugs that block methylation or the tumor-promoting effects caused by methylation, thus preventing cancer from ever developing. Several members of Dr. Grady’s lab focus their research on a protien called TGF-beta receptor type 2, a protein often found to be abnormal in colorectal cancer patients that have methylated genes in their tumors. Scientists suspect that abnormalities in the TGF-beta receptor are one of the causes for colon polyps turning into colon cancer.

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