Sonoporation for Augmenting Chemotherapy of Pancreatic Ductal Adenocarcinoma

Abstract

Pancreatic cancer is the third most common cancer diagnosed in the United States, with more than 53,000 new cases in 2017. It is the fourth leading cause of cancer-related death in both men and women. Nonetheless, there has been no significant improvement in survival for pancreatic ductal adenocarcinoma (PDAC) patients over the past 30+ years. For this reason, there is a considerable and urgent clinical need to develop innovative strategies for effective drug delivery and treatment monitoring, resulting in improved outcomes for patients with PDAC. This chapter describes the development of contrast-enhanced ultrasound image-guided drug delivery (CEUS-IGDD or sonoporation) to be that method and to translate it from the lab to the clinic. The initial clinical focus has been on a Phase I clinical trial for enhancing the effectiveness of standard chemotherapeutics for treatment of inoperable PDAC, which demonstrated a median survival increase from 8.9 months to 17.6 months in ten subjects augmented with sonoporation compared to 63 historical controls (p = 0.011). Recent efforts to optimize this platform and move forward to a larger Phase II clinical trial will be described.