Sonoporation for Augmenting Chemotherapy of Pancreatic Ductal Adenocarcinoma

Methods Mol Biol. 2020:2059:191-205. doi: 10.1007/978-1-4939-9798-5_9.

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.

Keywords: Augmented chemotherapy delivery; Contrast-enhanced ultrasound imaging; Human clinical trial; Pancreatic ductal adenocarcinoma; Sonoporation.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Animals
  • Carcinoma, Pancreatic Ductal / diagnostic imaging*
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Carcinoma, Pancreatic Ductal / pathology
  • Contrast Media / administration & dosage
  • Contrast Media / chemistry
  • Drug Delivery Systems / methods*
  • Female
  • Humans
  • Male
  • Mice
  • Microbubbles
  • Pancreatic Neoplasms / diagnostic imaging*
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Ultrasonography / instrumentation
  • Ultrasonography / methods*
  • Xenograft Model Antitumor Assays

Substances

  • Contrast Media