EXTH-27. ASSESING THE EFFECT OF ELECTRIC FIELD THERAPY ON PATIENT DERIVED GLIOMA STEM CELL LINES AND GLIOMA INFILTRATING CEREBRAL ORGANOIDS

Abstract

Abstract Glioblastoma (GBM) is the most aggressive primary brain tumour in adults. Electric field therapy (EFT) is a new cancer treatment applied after safe maximal tumour resection that interferes with cancer cell division, slowing tumour recurrence and prolonging life. In GBM patients, this therapeutic modality has demonstrated an increase in median survival from ~16 to ~21 months. This study aimed to assess and decipher the effectiveness of EFT on patient-derived glioblastoma stem cell lines (GSC) as well as on advanced Glioma infiltrating cerebral organoid models (GLICOs). To achieve the project goals, we used a novel In-vitro EFT stimulation apparatus to test stimulation parameters on multiple patient-derived GSC lines as well as GLICO models derived from them. We used advanced microscopy and transcriptomic sequencing to visualize and decipher the causal effect of our stimulation regime on the in-vitro models. We observe a strong effect of our EFT regime on multiple GSC lines as well as on GLICOs when compared to their controls. Transcriptomic analysis showed multitude of differentially expressed mRNAs between the treated and control samples with multiple pathways being dysregulated from nuclear proteins, cell mitosis-related events and activation of non-apoptotic mediated programmed cell death pathways indicating a novel mechanism of action. Advanced causal inference studies using the data also provided novel insights on combinatorial therapies that could enhance the efficacy of the treatment. This study provides novel understanding of the mechanism of EFT with potential for optimised treatment regimens for GBM patients.