Pancreatic cancer is on course to become the No. 2 cancer killer in the United States. To save more lives, researchers at Oregon Health & Science University have set out to reach the most vulnerable people; work with them to develop a reliable blood test to reveal early signs of the cancer; and validate new scanning techniques to locate and classify suspicious lesions for timely treatment.
The National Cancer Institute awarded the OHSU team a $3.8 million grant for this work, and they were made a member of the NCI’s Pancreatic Cancer Detection Consortium.
“We can move fast as part of this national consortium,” said principal investigator Rosalie Sears, Ph.D., a professor of molecular and medical genetics at the OHSU School of Medicine.
Sears and Brett Sheppard, M.D., are co-directors of the Brenden-Colson Center for Pancreatic Care at OHSU, and members of the OHSU Knight Cancer Institute.
“Our progress is really accelerating, and I think we have a huge opportunity to make an impact on high-risk populations,” said Sheppard, one of three other principal investigators and a professor of surgery at OHSU.
Over the past decade, the five-year survival rate for pancreatic cancer patients increased from 6% to 12%. Chances of surviving remain low because most patients are diagnosed after tumors have spread. For those diagnosed at the earliest stage, five-year survival rates can exceed 80%.
“If you can just pick up these people early, you can change the whole game,” Sheppard said.
Three-pronged strategy
Screening tests for cancer must be highly sensitive to not miss dangerous tumors, but also highly specific to avoid false alarms and unnecessary interventions. The OHSU team is working with a blood test that looks for pancreatic cancer by analyzing the variety of proteins that are contained in particles shed by cells. The microchip-based test requires only small amounts of blood and uses machine learning to identify cancer signatures. Stuart Ibsen, Ph.D., an assistant professor of biomedical engineering in the OHSU School of Medicine, and a faculty member in the Cancer Early Detection Advanced Research (CEDAR) Center at the OHSU Knight Cancer Institute, is collaborating on this work.
To follow up after a blood test indicates pancreatic cancer, the team is developing a magnetic resonance imaging protocol to find and characterize potential tumors. The magnetic resonance fingerprinting method measures inflammation and fibrosis — or thickening of tissue — as indicators of pre-cancerous growth and early-stage pancreatic cancer. Co-principal investigator Alexander Guimaraes, M.D., Ph.D., a professor of diagnostic radiology in the OHSU School of Medicine, OHSU Knight Cancer Institute, is heading up the imaging studies.
To make it all work will require a large number of people who are at risk of pancreatic cancer to volunteer as research subjects. The OHSU team is able to draw upon a large, statewide cohort developed by the Knight Cancer Institute: the Healthy Oregon Project, which has been providing no-cost genetic screening to thousands of people. The project is led by Jackilen Shannon, Ph.D., a professor in the Division of Oncological Sciences, OHSU School of Medicine, OHSU Knight Cancer Institute and CEDAR member.
Shannon and Gregory Coté, M.D., M.S., a medical oncologist with Massachusetts General Hospital and a co-principal investigator on the NCI grant, are leading an effort to understand and address barriers to cancer screening among members of minority communities, particularly those who suffer disproportionally from pancreatic cancer.
“It’s critically important to figure out how we can reach underserved communities and underrepresented populations, because across the U.S. they are not being screened and they're not entering early detection trials,” Sears said.
The researchers aim to enroll people with a family history of pancreatic cancer or a genetic test that has revealed mutations known to increase risk. They are also recruiting people at risk because they have pancreatic cysts that are detected incidentally by imaging.
Beyond the proposed research, OHSU has developed several resources at the Brenden-Colson Center that will be valuable to other institutions in the national consortium, which includes Dana Farber Cancer Institute at Harvard Medical School, Johns Hopkins University, Stanford University, the University of Texas MD Anderson Cancer Center, among others.
At OHSU, the Oregon Pancreas Tissue Registry has enrolled more than 3,700 patients. The OHSU Pancreatic Cancer Early Detection (PRECEDE) consortium has enrolled more than 100 high-risk individuals, and the OHSU High Risk Pancreatic Cancer Screening clinic has served more than 750 patients who have completed at least one screening test.
“We’ve built a lot of momentum,” Sheppard said. “We bring a lot of science to the consortium.”
The OHSU team is funded by the National Cancer Institute of the National Institutes of Health under Award Number U01CA278923