Dr. Brian Lewis is a faculty member in the Program for Gene Expression and Function and the Program for Molecular Medicine here at UMass Medical School. His primary research interest is in molecular oncology; however, his research is contributing to understanding the link between pancreatic cancer and diabetes.

As a post doctorate fellow, first at the National Institutes of Health in Bethesda, Maryland, then at Memorial Sloan-Kettering in New York, Dr. Lewis was interested in developing mouse models for the study of human cancer.  He discovered that there was no model for the study of pancreatic cancer, and the risk of developing pancreatic cancer may be higher for diabetics, relative to the general population.  As Dr. Lewis explains,

“Over 50% of the United States population over the age of 50 harbors precursor PanIN lesions as determined by autopsy.  We also know that newly diagnosed diabetics of that age have an increased risk of developing pancreatic cancer.

The key question is whether the metabolic state of the diabetic patient - high blood glucose, high blood insulin - promotes the progression of incipient disease.”

Funding from the DERC’s Pilot and Feasibility Study Program is helping Dr. Lewis to answer this question.

The Research:  Effect of Diabetes on Pancreatic Cancer Initiation and Progression

By combining somatic pancreatic cancer mouse models developed in his laboratory (Lewis et al, G&D 17:3127-38) with a high-fat induced model of diabetes, Dr. Lewis is determining whether diabetic mice develop pancreatic tumors earlier than than non-diabetic littermates and whether the tumors in diabetic mice progress more quickly, as evidenced by the tumor grade (how severe the cancer cells look under a microscope) and the presence of tumor metastases (whether it has spread to other areas).

He is exploring the potential mechanisms by which diabetes may contribute to the onset and progression of pancreatic cancer.  This exploration includes examining tumor tissue samples and tumor-derived cell lines, the status of several molecules such as K-Ras (a type of protein-encoding gene which has been implicated in the onset and development of cancer) and signaling pathways known to contribute to pancreatic malignancy, including the transforming growth factor beta and epidermal growth factor receptor.

Dr. Lewis knows that the question of whether diabetes contributes to the initiation and progression of pancreatic cancer is of significance to patients with diabetes,

“By understanding the relationship between the diabetic metabolic state and the initiation and progression of pancreatic cancer; we may be able to provide diabetes patients with important information about their potential cancer risk that they can discuss with their physicians. Awareness of the issue may lead to more heightened awareness of the symptoms of pancreatic cancer which are often non-specific, such as abdominal pain and jaundice.”

The DERC-supported research conducted by Dr. Lewis is a start to understanding this potential complication of diabetes and ultimately may lay the groundwork for new and better treatments.