Researchers Make Discoveries in Fight against Pancreatic Cancer

Article date: November 3, 2011

By Stacy Simon
New discoveries are giving researchers hope about the future of detection and treatment of pancreatic cancer, one of the most difficult cancers to find early and treat effectively. During the past 10 years, the American Cancer Society has invested more than $60 million in more than 150 research studies into the prevention, early detection and treatment of pancreatic cancer.
One reason pancreatic cancer is so hard to find early is that the pancreas is located deep inside the body, making it nearly impossible for health care providers to see or feel tumors during routine exams. Patients usually have no symptoms until the cancer has already spread to other organs. Only about 5% of patients live 5 years past diagnosis, which is among the lowest survival rates for any cancer.
Right now, there are no reliable routine screening tests to look for pancreatic cancer in people without symptoms. Researchers have found some substances that pancreatic cancer cells release into the blood, but by the time levels of these substances are detectable, the cancer is no longer in its early stages. Blood tests for these substances are used mainly to help monitor the course of the cancer in someone already known to have it, rather than to look for cancer early.
Researchers have also found that pancreatic cancer cells often contain certain changes in their DNA. Current research is exploring ways to develop screening tests that use new DNA and blood markers to detect pancreatic cancer earlier, when it’s easier to treat.

DNA Markers

American Cancer Society-funded research professor Burt Vogelstein, MD, at Johns Hopkins University, has found compelling evidence linking certain DNA changes to pancreatic cancer. Ralph Hruban, MD, also at Johns Hopkins, has identified certain genes (pieces of DNA) that are frequently damaged in pancreatic cancer, including KRAS, CDKN2A, p53, and SMAD4. Changes to these genes and others are believed to cause pancreatic cancer.
Building on the DNA research, doctors at the Mayo Clinic are studying a new way to test for pancreatic cancer in patients’ stool samples, recently publishing their research online in the journal Cancer. Their study focused on detecting DNA changes in stool samples of 123 patients, 58 diagnosed with pancreatic cancer and 65 who were not diagnosed with cancer.
"We found that a marker was reliably detected in both tissue samples and in the stools of pancreatic cancer patients, and that it compared favorably with another kind of marker - the mutation of a gene called KRAS," says John Kisiel, M.D., Mayo Clinic gastroenterologist, who presented the study's findings at a recent meeting. "When we looked at those two markers together, the combined accuracy of both markers was significantly better than with either marker alone."
The screening detected the markers regardless of the stage of cancer or the location of the cancer within the pancreas. If confirmed by future studies, these findings may lead to more early detection of pancreatic cancer, which could significantly increase the survival rate for those who have the disease. The stool tests are also noninvasive, and samples could be collected by patients at home and sent to their doctor, without an office or clinic visit.

Blood Tests

Researchers at the University of Michigan Comprehensive Cancer Center have identified a protein that could lead to a blood test to detect pancreatic cancer at an earlier, more treatable stage.
"One of the difficulties in screening for pancreatic cancer is distinguishing it from other conditions, such as diabetes or pancreatitis. There is not a good marker currently that can do that. Ultimately, we need to detect earlier stages of pancreatic cancer that can be operated on and treated. Once the cancer reaches advanced stages, it becomes difficult to treat," said senior study author David M. Lubman, Ph.D.
In this study, published online in the Journal of Proteome Research, Lubman and colleagues looked at proteins in the blood, and identified one, haptoglobin, that changes its structure depending on whether it appears in pancreatic cancer, non-cancerous diseases, or normal blood serum.
The researchers will continue to refine this marker to allow them to better and more reliably distinguish early stage pancreatic cancer. They will also begin testing this approach in larger samples. This test is not yet available to patients.
"Screening for pancreatic cancer would not be done through the general population because it's a fairly rare cancer. Rather, a test like this could potentially be used to screen people who are in high risk groups – those with a family history of pancreatic cancer, people who are obese or smoke, and people who have long-term diabetes or pancreatitis," Lubman says.

Delivering Treatment

Another active area of research involves the treatment of pancreatic cancer. The American Cancer Society is currently investing more than $17 million in 31 research projects with a significant emphasis on new treatment options.
For example, former American Cancer Society grantee Dan Van Hoff, MD at the Translational Genomics Institute and American Cancer Society Research Professor Ronald DiPinho, MD at Harvard University have shown that pancreatic tumors are often surrounded by a dense layer of fibrous tissue. This tissue may make it hard for many chemotherapy drugs to reach the tumor, which may help explain why chemotherapy is often not effective in treating this type of cancer.
William Phelps, PhD, American Cancer Society Director of Preclinical and Translational Cancer Research says researchers are gaining a better understanding of that tissue. Phelps says this understanding could help researchers figure out how to treat pancreatic tumors more effectively, perhaps by designing drugs that more effectively get by this barrier.
Reviewed by: Members of the ACS Medical Content Staff

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Researchers Make Discoveries in Fight against Pancreatic Cancer