Physical and Chemical Enhancement of and Adaptive Resistance to Irreversible Electroporation of Pancreatic Cancer

Irreversible electroporation (IRE) can be used to treat cancer by electrical pulses, with advantages over traditional thermal approaches. Here we assess for the first time the IRE response of pancreatic cancer, one of the deadliest forms of cancer, both in vitro and in vivo. We demonstrate that both established and primary cancer cell lines can be destroyed by IRE, but with differential susceptibility and thresholds. We further demonstrate in vitro that viability for a given IRE dose can vary with the local chemistry as outcomes were shown to depend on suspending medium and reduction of glucose in the media significantly improved IRE destruction. Data here also demonstrate that repeated IRE treatments can lead to adaptive resistance in pancreatic carcinoma cells thereby reducing subsequent treatment efficacy. In addition, we demonstrate that physical enhancement of IRE, by re-arranging the pulse sequences without increasing the electrical energy delivered, achieve reduced viability in vitro and decreased tumor growth in an in vivo xenograft model. Together, these results show that IRE can destroy pancreatic cancer in vitro and in vivo, that there are both chemical and physical enhancements that can improve tumor destruction, and that one should guard against adaptive resistance when performing repeated treatments.