Pancreatic Cancer Research

Pancreatic cancer is the fourth leading cause of cancer death in the United States, claiming a higher percentage of its victims than any other form of cancer. Its five-year survival rate of three percent makes it virtually incurable

Mayo Clinic researchers in pancreatic cancer are focused on discovering and developing new therapies for patients with pancreatic cancer. Their research spans a wide range of areas with the key theme of accelerating the delivery of new treatments to patients with pancreatic cancer. Notably, Mayo Clinic Cancer Center is one of three national institutions that have been awarded a Specialized Program of Research Excellence (SPORE) award for pancreatic cancer research.

Some current areas of focus for GI Program researchers studying pancreatic cancer include:

Genetics

• Cutting-edge genetic analyses of surgically resected cancers, that focuses on genetic and biochemical approaches to identify diagnostics and molecular targets for the development of new therapies for pancreatic cancer.
• Mouse models of pancreatic cancer are also being developed to understand how genetic alterations found in the human disease contribute to the development and progression of pancreatic cancer. Additionally, these mouse models can be used to examine the effects of novel therapeutics in the treatment of cancer, as well as for biomarker discovery. Fergus Couch, Ph.D., is investigating the contribution of the DNA repair protein BRCA2, which is mutated in some families with inherited forms of pancreatic cancer, in the regulation of the development of pancreatic cancer using a mouse model.
• Genetic studies that look at why pancreatic cancer runs in some families are very important in solving the puzzle of pancreatic cancer. It is hypothesized that these individuals carry mutations in a gene that predisposes them to pancreatic cancer. Gloria Petersen, Ph.D., is spearheading studies aimed at identifying these pancreatic cancer-related genes. The identification of these genes, will lead to new techniques to diagnose and treat this cancer.

Biomarker Discovery

• Research led by Suresh Chari, M.D. has uncovered a link between late-onset diabetes and pancreatic cancer. The long-term goal of his research is to make screening for sporadic pancreatic cancer feasible and cost-effective. The focus of the research is on the use of hyperglycemia (higher than normal blood glucose levels) and diabetes as markers of undiagnosed pancreatic cancer. In pancreatic cancer hyperglycemia and diabetes occur very commonly (in up to 80 percent of patients) and are often evident many months prior to the diagnosis of pancreatic cancer. Individuals with new-onset diabetes aged > 50 years have approximately an 8 fold higher risk of having pancreatic cancer compared to the general population. Currently efforts are underway to determine the mechanism by which pancreatic cancer causes diabetes and to identify markers that can distinguish diabetes due to pancreatic cancer from the more common type 2 diabetes.

Molecular Biology

• Scientists have identified several proteins that are critical for pancreatic cancer cells to proliferate and survive. One such family of proteins is the Rac proteins, which have been identified to have similar roles in other cancers, making them attractive targets for researchers. The research team led by Daniel Billadeau, Ph.D. is searching for small molecules can inhibit Rac protein function, thus stopping cancer proliferation, survival and migration.
• Recent studies have also identified the kinase GSK-3_ as a key regulator of pancreatic cancer cell proliferation and survival. Dr. Billadeau and George Kim, M.D., are currently designing a clinical trial in which a GSK-3 inhibitor will be used to treat unresectable metastatic pancreatic cancer.
• The laboratory of Raul Urrutia, M.D., is investigating the molecular mechanisms by which the chemokine SDF-1_ and its receptor regulate pancreatic cancer cell motility and development of new blood vessels (angiogenesis). His laboratory is also interested in understanding the mechanisms that contribute to the transcriptional silencing of genes in cancer that control normal cell proliferation.
• Another interesting pathway that is normally only activated during embryonic development, but is aberrantly activated in pancreatic cancer is a pathway known as hedgehog. This receptor/signaling complex is involved in the regulation of pancreatic cancer cell survival and is the research focus of Martin Fernandez-Zapico, M.D. He is investigating how this pathway contributes to the survival of pancreatic cancer cells and is also using novel small molecule inhibitors of this pathway to determine their efficacy in the treatment of pancreatic cancer.
• The mucin MUC1 is overexpressed in pancreatic cancer and is a potential target for vaccine therapy. Using mouse models and immune-modulating agents, Pinku Mukherjee, Ph.D., is attempting to augment MUC1-target vaccine therapy for the treatment of pancreatic cancer.

Pancreatic Cancer Genetic Epidemiology (PACGENE) Consortium
Mayo Clinic scientists are also working with other scientists throughout the U.S. to identify susceptibility genes for pancreatic cancer, and to learn whether these genes manifest through exposure to cigarette smoking. The large research study is being conducted by the Pancreatic Cancer Genetic Epidemiology (PACGENE) Consortium and is funded by the National Cancer Institute. Led by Dr. Petersen, the purpose of the study is to compare any inherited or genetic characteristics from blood and tissue specimens collected from individuals who have been diagnosed with pancreatic cancer and the blood and tissue of their family members. They are studying responses to a family history and lifestyle survey and biospecimens (blood and tissue) to look for patterns of inheritance of cancer risk.