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. Mitochondria function is also especially important under low nutrient conditions and we seek to target this metabolic vulnerability in pancreatic cancer. We have received funding from the American Cancer Society and the NCI to pursue these lines of investigation.
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 with the hope of extended patient survival.
Pancreatic cancer-associated depression
Depression is more common in cancer than the general population, and amongst cancers, is the most common in pancreatic cancer. We will perform a randomized trial in patients with pancreatic cancer and randomized patients to an anti-depressant or placebo in order to try and reduce depression. Additionally, we study the biology of pancreatic cancer-associated depression, and believe it is directly related to increased tryptophan catabolism.