Pancreatic cancer metabolism
Pancreatic cancer cells are poorly perfused, and live in a particularly harsh microenvironment characterized by low nutrient and oxygen levels. Normal cells however are well perfused and therefore have abundant nutrient availability. We are studying the molecular mechanisms that allow pancreatic cancer cells to adapt low nutrient conditions. Through investigations in tissue culture and mouse models of pancreatic cancer, we have shown that a regulatory molecule, HuR, supports pancreatic cancer survival under harsh conditions, and this is largely due to its regulation of the metabolic enzyme, isocitrate dehyrdrogenase (IDH1). We are interested in developing novel therapies that target this molecular interaction in order to render pancreatic cancer cells susceptible to stressful metabolic conditions. This research is funded by the American Cancer Society and the Coleman-Bruntel Pancreatic Research Fund.
Live organoid biobank of pancreatic cancer specimens
We have acquired expertise in generating patient-derived cultures from patient biopsies with more than a 90% success rate, including samples from resected specimens, endoscopic biopsies, and percutaneous biopsies. As a result, we are generating a vast biobank that will facilitate biologic investigations and experimental therapeutic research. We aim to translate this research into novel personalized approaches to pancreatic cancer care, where therapies can be tested on patient derived tumors, with implications for therapeutic decisions in the clinic.
Clinical trial investigating the risk of intraoperative tumor shedding with pancreatic surgery
There has been little attention directed towards the possibility that cancer cells are spread at the time of surgery. However, there are compelling data from the East Asian literature that support this possibility. These studies have demonstrated that lavage with saline or distilled water reduces recurrence risk from cancer cell shedding in other gastrointestinal cancers, and can improve cancer-specific survival. In order to directly address this question for patients with pancreatic cancer, we have initiated a randomized multi-institution clinical trial in which patients are treated either without lavage at the time of resection, or with high volume lavage to the surgical bed with either saline or water. Patients will have peritoneal washings at the start of the operation, after resection, and after lavage, in order to assess for cytologic evidence of cancer cell dissemination.
Gene therapy to treat pancreatic cancer
We have had NIH to study promoter-driven diphtheria toxin therapy that directly targets pancreatic cancer cells. We are testing a novel biodegradable nanoparticle to deliver genetic payloads specifically to pancreatic cancer in animal models.