Genes encode proteins and proteins dictate cell function. Therefore, the thousands of genes expressed in a particular cell determine what that cell can do. Changes in cancer gene expression can be influenced by epigenetic factors. Epigenetics is the study of the biological mechanism that turns a cell “on or off.” Understanding the epigenetics of a tumor can lead to new treatments. Studies by our Lustgarten–funded researchers at Dana-Farber Cancer Institute, Johns Hopkins and the Salk Institute for Biological Studies are significantly advancing the research in this area.
David Pellman, M.D., Dana-Farber Cancer Institute, is studying why genome catastrophes, a phenomenon by which up to thousands of clustered chromosomal rearrangements (or abnormalities) occur in a single event, are so common in pancreatic cancer. He is working to identify the underlying causes and potential therapies for treating genome catastrophes to prevent pancreatic tumors from developing. Dr. Pellman and his team are using pancreatic organoid cultures to model the different stages in pancreatic cancer development.
Andrew Feinberg, M.D., and his team at Johns Hopkins University School of Medicine identified new epigenetic defects, or changes in the genes that occur during metastasis. By studying these defects, the team is creating compounds to prevent the tumor from spreading beyond the pancreas to organs such as the liver. If the tumor can be contained to the pancreas there is a much better chance at long-term survival.
A cancer biomarker refers to a molecule or protein secreted by a tumor or a specific bodily response indicative of the presence of cancer in the body. One of these cancer biomarkers that impacts pancreatic cancer is the leukemia inhibitory factor, a normal protein found in cells. However, in pancreatic cancer, it’s overly produced, encouraging tumor growth and inhibiting the body’s immune response to the tumor. Tony Hunter, Ph.D., and his team at the Salk Institute for Biological Studies are working to determine if this protein can be used as a biomarker and how it can influence the immune system to target treatments. This work may also have implications for earlier detection.
Vitamin D Receptor
Ronald Evans, Ph.D., Salk Institute for Biological Studies, is working to better understand the epigenetic factors that dictate the behavior of both the pancreatic cancer cells and the pancreatic stromal cells in hopes of identifying key signaling factors that can be targeted therapeutically. A chemically modified version of vitamin D (called paricalcitol) controls the “shut-off” valve on the gene, giving hope for a new way to slow tumor progression. Dr. Evans’ research shows that if patients’ tumors have this vitamin D receptor, they could be eligible for treatment with paricalcitol as part of their therapy. Our first trials in patients are already underway.