Mechanism and treatment of pancreatic tumor progression: Pancreatic cancer is a notoriously deadly tumor type, with only 6% of patients surviving to 5 years after diagnosis. There is a lack of effective methodology for early detection and front line therapy has not evolved at the pace of other tumor types. Tumor development increases with age, and often is not diagnosed until late stage tumor progression when the cancer is difficult to treat.
Dr. Altomare’s research laboratory uses mouse models that have a genetic susceptibility to develop pancreatic cancer in order to understand cellular and/or protein signaling pathways, and to test overall relevance to the human disease. The group is interested in understanding ways to manipulate tissue damage, changes to cytokines or growth factors that mediate protein signaling pathways and to analyze how to shift the infiltration of immune cells in response to cellular damage. The goals are to define factors leading to increased risk for pancreatic cancer and to intervene with a molecular targeted therapy that will delay progression of the disease.
Preclinical response of human ovarian cancer to immune cell therapy (collaborator, Alicja J. Copik): Approximately 80% of ovarian cancer patients will respond to surgery and first-line chemotherapy. However, patients frequently relapse with chemotherapy resistant disease. The challenge is to develop novel therapeutic strategies that can be effective in these patients to extend progression-free and overall survival.
The Altomare research group is assessing the ability of innate immune cells, namely natural killer (NK) cells, to facilitate ovarian tumor cell killing. The studies use mice implanted with human ovarian tumor cells followed by treatment with human blood cells. Response of the tumors, expansion of the immune cells, as well as persistence and homing characteristics of the immune cells are tracked in order to understand the biology and usefulness of a similar therapy for ovarian and other cancers.
Novel cancer therapies which target polyamine metabolism (collaborator, Otto Phanstiel): Pancreatic and other tumor types frequently have altered metabolic pathways that should make them more susceptible to certain treatments compared to normal cells. One strategy is to test the usefulness of targeting the tightly regulated polyamine pathways.
Dr. Altomare’s laboratory uses pancreatic cancer cells implanted in the pancreas of a mouse in order to test the effectiveness of newly identified synthetic polyamine- or non-polyamine structured reagents at blocking tumor progression. The premise is that a combination therapy involving an inhibitor of polyamine biosynthesis (difluoromethylornithine, DFMO) and an inhibitor of polyamine transport will be more effective than a single agent against pancreatic cancers. The goal is to define effective types of polyamine pathway inhibitors and to determine if these strategies can be used to improve survival.