Abstract 6640: Zap! Irreversible electroporation in pancreatic cancer cells induces proinflammatory cell death and improves progression free survival

Abstract

Abstract Pancreatic cancer is the third leading cause of cancer-related death due to its late diagnosis, few treatment options, and extremely low survival rates due to its immunosuppressive microenvironment. Irreversible electroporation (IRE),is a tumor non-thermal ablation technique that applies high-voltage electrical pulses to permeabilize the cell membrane that is irreversible and leads to necrotic cell death. IRE has had strong success in clinical trials nevertheless, little is known about the effect of IRE beyond the initiation of cell death in the tumor tissue. We hypothesize that IRE can not only induce cell death by membrane disruption to facilitate a proinflammatory microenvironment but also causes death via cell cycle arrest. We utilized in-vitro, and immunocompetent in-vivo murine models to investigate changes to pancreatic cancer and the tumor microenvironment. Our findings show that treating the cells with an increasing voltage of IRE induces more cell death. We observed cell cycle arrest in the G1 phase which may have been caused by DNA damage. There was upregulation of DNA damage repair machinery in the treated samples. Our histopathology data suggests increased necrosis on the tumor treated with IRE, as also PCR array analysis showed more proinflammatory cell death caused by pyroptosis. Finally, we demonstrated a reduction in the tumor size and a better survival rate aftertreatment. Our data suggest that Irreversible electroporation has a promising future in inducing proinflammatory type of cell death in the tumor and benefits increased patient survival. More investigation is needed to define ideal parameters for the electrical pulses and device development for tumor ablation in larger animals like porcine models. Citation Format: Manali Powar, Khan Mohammad Imran, Irving C. Allen, Rafael V. Davalos, Zaid Salamah, Kenneth Aycock, Rebecca M. Brock, Sheryl Coutermarsh-Ott, Katie Orr. Zap! Irreversible electroporation in pancreatic cancer cells induces proinflammatory cell death and improves progression free survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6640.