U of M discovery breaks down resistance of pancreatic cancer cells to therapy

This is the first laboratory study to examine the ability of triptolide, which has been used as a natural medicine in China for hundreds of years, to induce pancreatic cancer cell death. Ashok Saluja, Ph.D., University of Minnesota Medical School and Cancer Center, led the laboratory research team that made this discovery. The findings are published in the October issue of Cancer Research, a journal of the American Association of Cancer Research. The National Cancer Institute funded this research study.

"We need to do more research to test and validate our laboratory findings, but the results of this study give us reason to think that hope might be in sight for pancreatic cancer patients," said Saluja, vice chair for research at the University's Department of Surgery and a pancreatic cancer researcher for more than 25 years. A pancreatic cancer surgeon and researcher Selwyn Vickers, M.D., chair of the University of Minnesota's Department of Surgery and co-investigator on this study, seconds Saluja that this finding could develop into an effective therapy for patients suffering from pancreatic cancer.

Pancreatic cancer affects the pancreas, an organ deep within the body that is close to the backbone and vital organs. Unlike some other cancers, pancreatic cancer shows few early symptoms and is therefore usually well advanced when found. It is difficult to treat, and almost impossible to cure. Of the 37,000 people in the United States diagnosed annually with pancreatic cancer, 550 in Minnesota, more than 36,000 of them will die within two years. About 50 percent of them die within three to four months of diagnosis.

According to Saluja, pancreatic cancer cells are aggressive and tough, and the body cannot get rid of them in the usual way it discards unneeded and abnormal cells. Pancreatic cancer cells are also highly resistant to currently available chemotherapy treatments.

In previous studies, Saluja and his colleagues identified a protein called heat shock protein 70 (HSP70) as the culprit that prevents the breakdown of pancreatic cancer cells. They found that pancreatic cancer cells have significantly higher levels of HSP70 and that the protein serves as a survival mechanism for the cells.

In these latest experiments, Saluja and his team discovered that triptolide can invade HSP70 and attack pancreatic cancer cells.

"Several other research reports had indicated the effectiveness of triptolide against melanoma, breast cancer, bladder cancer, and stomach cancer, but no one before us has investigated it in connection with pancreatic cancer," Saluja said. "Our goals were to assess triptolide's viability in causing cells to die, its impact on stopping the growth and spread of the cells, and its ability to reduce the levels of HSP70 in pancreatic cancer cells.

"We found that mice that received triptolide had decreased pancreatic cancer growth, significantly decreased disease spread, and substantially reduced the HSP70 levels," he said. "By comparison, mice that did not receive triptolide had extensive pancreatic cancer growth and invasion into adjacent organs, including the spleen, liver, kidney, and small intestine."

The next step for Saluja and his team is to refine the compound so that it can be tested in humans. His goal is to start clinical trials involving patients with pancreatic cancer in about two years.

Researchers working with Saluja on this study include P.A. Phillips, V. Dudeja, J. McCarroll, D. Borja-Cacho, R. Dawra, and S. Vickers, all with the University of Minnesota, and W. Grizzle with the University of Alabama, Birmingham.

The Academic Health Center is home to the University of Minnesota's six health professional schools and colleges as well as several health-related centers and institutes. Founded in 1851, the University is one of the oldest and largest land grant institutions in the country. The AHC prepares the new health professionals who improve the health of communities, discover and deliver new treatments and cures, and strengthen the health economy.

The University of Minnesota Cancer Center is part of the University's Academic Health Center. It is designated a Comprehensive Cancer Center by the National Cancer Institute. To learn more about the Cancer Center and cancer, call 612-624-2620 or toll-free in Minnesota, Iowa, Wisconsin, and the Dakotas at 1-888-CANCER MN (1-888-226-2376); or visit www.cancer.umn.edu.

Media Contacts:

Mary Lawson, Cancer Center, 612-624-6165, mlawson@umn.edu
Sara Buss, Academic Health Center, 612-626-7037, buss@umn.edu