Researchers Identify Biomarkers of Early-stage Pancreatic Cancer in Mice and Man

A multicenter team of researchers has identified a panel of proteins linked to early development of pancreatic cancer in mice that applies also to early stages of the disease in humans – a breakthrough that brings scientists a significant step closer to developing a blood test to detect the disease early, when cure rates are highest.

The findings, by senior author Samir “Sam” Hanash, M.D., Ph.D., of Fred Hutchinson Cancer Research Center, will be published in the June 10 issue of PLoS Medicine, a freely available, open-access online journal. Investigators from Massachusetts General Hospital, University of Michigan and Belfer Institute for Innovative Cancer Science at Dana-Farber Cancer Institute collaborated on the research.

“Our team identified, for the first time, protein changes associated with early-stage pancreatic-tumor development in genetically engineered mice that were also found to be associated with the presence of the disease in humans at an early, pre-symptomatic stage,” said Hanash, head of the Hutchinson Center’s Molecular Diagnostics Program. Hanash is an international leader in the field of proteomics, which seeks to identify clinically relevant trace proteins, or biomarkers, that are leaked by tumors into the blood. Scientists believe that such proteins could be used in screening blood tests for early and more accurate detection of cancer and other diseases.

“Our findings represent a breakthrough in the application of advanced proteomic technologies and mouse models to cancer-biomarker discovery,” said Hanash, also a member of the Hutchinson Center’s Public Health Sciences Division.

The five-biomarker panel, if developed into a commercial screening test, may be particularly useful when combined with a currently available test that measures a pancreatic-cancer biomarker called CA19.9, which is elevated in 80 percent of newly diagnosed patients but is not linked to asymptomatic, early-stage disease. Together, the biomarker panel and CA19.9 may significantly improve the detection of early-stage disease prior to the onset of symptoms and may also help better distinguish between cancer and pancreatitis, a noncancerous, inflammatory condition.

Early detection of cancer is crucial for long-term survival. Most solid tumors can be cured 90 percent of the time if they’re detected and treated early, whereas cure rates for late-stage cancer are about 10 percent. Early detection is particularly relevant to pancreatic cancer, which is the fourth-leading cause of cancer death in the United States, with a five-year survival rate of only 3 percent. Because the disease is asymptomatic in the early stages, most patients are not diagnosed until the cancer has spread beyond the pancreas, which contributes significantly to the poor long-term survival rate.

“There is a substantial challenge in studying the early molecular changes in pancreatic cancer because most patients are diagnosed with advanced-stage disease and so there is a lack of suitable specimens for biomarker discovery,” said paper co-author Nabeel Bardeesy, Ph.D., of the Massachusetts General Hospital Cancer Center.