Basic Research at Penn State Hershey Places Pancreatic Cancer Prevention on the Horizon

Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Usually detected at only the most advanced stages and with median survival time of only three to six months, it leaves little time for treatment or cure. This abysmal clinical outlook has fueled a great deal of research into the nature of pancreatic cancer, as well as key patient factors that place some people at increased risk of the disease.

According to Gail Matters, PhD, associate professor of biochemistry and molecular biology at Penn State Health Milton S. Hershey Medical Center, Penn State College of Medicine, “The link between patient factors like obesity, chronic pancreatitis, and a family history of pancreatic cancer have provided clues about underlying cellular and molecular pathologies. We know that certain normally-occurring peptides, like cholecystokinin (CCK), are found in elevated concentrations in mice that have been fed a high-fat diet. These peptides have a growth-factor-like effect on pancreatic tumor cells.”

Matters and her colleagues have focused on these molecules and their receptors as interesting targets for new treatments. “By controlling the ability of CCK or gastrin to act at their receptors, we may be able slow or prevent malignant pancreatic cancer cell growth and metastasis,” notes Matters. Based on preliminary data obtained in Matter’s lab, a grant aimed at exploring the relationship between obesity, peptides like CCK and gastrin, and pancreatic cancer is being considered for approval by the National Cancer Institute.

In one recent study, conducted in transgenic mice prone to pancreatic tumor development, Matters examined the effect of CCK receptor blockade on tumor grade, inflammation and fibrosis. In these mice, the oncogenic Kras allele is specifically activated in pancreatic cells, and by six to eight months of age about 10 percent of pancreatic lesions have developed into invasive adenocarcinomas. Matters explains, “When we placed proglumide (an orally available CCK type A and type B receptor antagonist) in their drinking water for four months, we saw a significant decreased in pre-cancerous lesion progression. Pancreatic tissue sections from proglumide-treated mice showed less fibrosis and blood vessels contained fewer tumor emboli. At some point in the future, it may be possible to use drugs that block CCK or gastrin receptors to prevent pancreatic cancer, particularly in patients we know to be at high risk for the disease.”

Gail Matters, PhD
Associate Professor of Biochemistry and Molecular Biology
Penn State College of Medicine
Email: glm14@psu.edu
Phone: 717-531-4098