As the fourth leading cause of cancer death in the United States, pancreatic cancer remains one of the most deadly forms of cancer. More than 90 percent of patients die within the first year of diagnosis. Recent advancements have had little impact, and a new approach is desperately needed.
Scientists have suggested the possibility of "starving" cancer cells to death by depriving them of a specific nutrient that they require for survival. Recent studies have demonstrated that most cells acquire mutations causing them to become addicted to a continual supply of nutrients to produce the energy needed for survival and proliferation. In most cancers, this nutrient is glucose.
Using modern tumor imaging, it is possible to monitor a tumor's glucose utilization and such tests are now routinely used in clinical practice. In most cases, the more glucose a tumor is using, the more advanced the tumor and the greater likelihood of spread. Similarly, if a tumor is using less glucose as a response to chemotherapy, then it is a good indication that the tumor is responding to treatment.
Pancreatic cancer presents a unique challenge because it is addicted to another molecule, glutamine, rather than glucose. Glutamine is an amino acid that helps build muscle mass and is used by some cells for energy. When cancer feeds or metabolizes excess amounts of gluatamine, it can lead to extreme weight loss by robbing other cells of this important nutrient, a condition from which many pancreatic cancer patients suffer. In addition, the waste that is a by-product of this process generates an intense reaction from surrounding normal cells, which then secrete growth factors that help tumor cells grow. Cancers that use excess glutamine are often resistant to standard forms of chemotherapy, another characteristic of pancreatic cancer.
Specific Research Goals:
- The goal of this Dream Team is to develop tests using advanced imaging techniques to determine what nutrients pancreatic cancer cells require to fuel their growth and survival. Understanding the cell's fuel supply will help scientists to develop more individualized treatments with fewer side effects.
- This Dream Team will immediately begin a series of clinical trials designed to deprive pancreatic tumors of crucial nutrients. The Team will test the drugs in combination with existing standard chemotherapy, with the hope to increase the percentage of pancreatic cancer patients surviving beyond one year while improving quality of life.
This SU2C Dream Team is conducting clinical trials to test new ways of cutting off the fuel supply to pancreatic cancer. One set of trials uses a drug to break through the tough coating surrounding the cancer so that a second drug can kill the cancer cells. This drug combination is showing positive preliminary results in actually shrinking tumors. Another effort is aimed at examining a tumor's metabolism to personalize treatment for individual patients so that the effectiveness of treatment is maximized and side effects are minimized. The team is also developing new ways to get images of pancreatic cancer, so that the tumor's response to treatment can be observed. This will make personalized treatment a reality for pancreatic cancer patients.
Jeffrey A. Drebin, MD, PhD, chair, department of surgery, University of Pennsylvania
Ronald M. Evans, PhD, professor, Salk Institute for Biological Studies
Daniel A. Laheru, MD, associate professor, medical oncology, Johns Hopkins University
Joshua D. Rabinowitz, MD, PhD, assistant professor of chemistry and integrative genomics, Princeton University