Pancreatic Cancer is a lethal malignancy with a very poor survival rate. Systemic intravenous chemotherapy administration is the first-line treatment for patients with unresectable pancreatic cancer; however, its responses are limited given issues related to limited drug concentration reaching the tumor, systemic toxicity and poor tumor penetrance. Our research aims to improve chemotherapy efficacy using locoregional delivery directly into pancreatic tumors, via its arterial blood supply, as well as modulating the stomal barrier around tumors.
In the United States, approximately 55,440 patients are diagnosed with pancreatic cancer each year. Pancreatic cancer is the fourth leading cause of cancer-related death and is expected to rise to second place by 2030. The majority of pancreatic cancer tumors (85%) are adenocarcinomas arising from the ductal epithelium (pancreatic ductal adenocarcinoma; PDAC). As most patients are diagnosed late and often have advanced disease, the overall 5-year survival rate for this disease is only 8% given that 80-85% of patients present late with advanced or even metastatic disease.
Systemic chemotherapy plays a central role in the treatment of pancreatic cancer diagnosed at all stages. Initially it was thought that increasing the dose of chemotherapeutics, like gemcitabine, would overcome these obstacles and enable the effective treatment of pancreatic cancer; especially since the therapeutic effects of such drugs have been shown to be dose-dependent in cell culture studies. However, clinical studies, in general, have shown that increasing the systemic dose of chemotherapeutics results in a higher incidence of systemic toxicity with often only a marginal increase in therapeutic benefit. Hence, to effectively
effectively treat tumors like pancreatic cancer, more targeted approaches are needed to ensure that drugs actually reach and penetrate into the tumor. Hence, we developed a novel and reproducible microsurgical technique to deliver therapeutics directly into pancreatic tumors, via its arterial blood supply, and showed in orthotopic rodent models that we can achieve comparable reductions in tumor growth with gemcitabine with considerably less dose when compared to conventional systemic intravenous administration of the drug. Current work is now examining the role of pulsed focused ultrasound (pFUS) to augment chemotherapeutic effects by using sound waves to transiently increase vascular permeability as well as modulate the immune microenvironment.