Grant: Operating Grant

Pancreatic cancer is an aggressive disease with an extremely high mortality rate, with only 5% of patients surviving past 5-years after diagnosis, ranking it as the fourth leading cause of cancer deaths. Less than 20% of the patients are eligible for surgical removal of the tumors, while the rest only benefit marginally in survival, as the standard-of-care gemcitabine chemotherapy is plagued by poor delivery of the drug to the tumor. This project is focused on developing an improved gemcitabine delivery technology for enhanced treatment of patients with inoperable and locally advanced pancreatic tumors. This group represents ~35% of the total number of pancreatic cancer patients and their prognosis gives them a median survival of just 9-10 months. We have developed an improved nanoparticle formulation (HaT) that reduces gemcitabine clearance by 50-fold from the blood of mice after intravenous injection, compared to the current drug solution given clinically. HaT is stable in the blood, but releases 100% of the drug load rapidly when heated to 40-42°C, leading to a 25-fold increase in delivery of gemcitabine to the locally heated tumor (43°C), compared to the clinical formulation in a mouse model. A single treatment of HaT combined with local heating completely regresses the tumor with manageable side effects. We plan to test the efficacy and toxicity in multiple pancreatic tumor models. The mode of action of this new treatment will also be elucidated. Finally, we will employ an ultrasound system that specifically heats pancreatic tumors, with precise temperature control under MRI guidance, to promote targeted drug delivery with the HaT formulation. The long term goal is to produce an enhanced treatment for patients with locally advanced pancreatic tumors.