Tumour Treating Electric Fields for non-invasive Treatment of Glioblastoma

Abstract

Glioblastoma is an aggressive and fatal cancer with a median overall survival of just 15 months. Tumour Treating Fields (TTF) is a non-invasive treatment which uses alternating electric fields to disrupt mitosis. Clinical trial data demonstrated a 4 month gain in overall survival with a combination of TTF and standard chemotherapy, yet studies investigating the effects of TTF as a monotherapy are underexplored. This study optimises TTF therapy using the model organism Drosophila melanogaster and live confocal microscopy. Drosophila is a suitable model for studying TTF parameter optimisation in a high throughput manner due to the synchronous and rapid rate of embryonic cell division in a non-cancerous model. Additionally, the well characterised Drosophila brain tumour model (brat) was used in this study to investigate the effects of TTF on brain tumours in living larvae. Using live confocal microscopy, TTF parameters were optimised to induce abnormal mitotic phenotypes in 100 percent of healthy Drosophila embryos, without impacting nervous system function. In the Drosophila brain tumour model and healthy cellularised embryos, TTF caused a duration dependent arrest of metaphase. TTF had no affect on the percentage of EdU positive cells in Drosophila brain tumours or in human patient-derived glioblastoma stem cells (GSCs) but EdU incorporation is reduced in immortalised glioma cells (U87MG). Conversely, Ki67 levels are reduced in GSCs but are unchanged in U87MG cells, suggesting cell type specific responses and sensitivity to TTF. Additionally, TTF treatment increases cell death in U87MG cells. This data provides evidence that TTF alone can work as an anti-cancer therapy and that it is a highly effective, safe cancer treatment.

Date of Award	2026
Original language	English
Awarding Institution	University of Plymouth
Sponsors	UKRI EPSRC & Zimmer and Peacock Ltd.
Supervisor	Shakil Awan (Director of Studies (First Supervisor)), Torsten Bossing (Other Supervisor), Jon Gil Ranedo (Other Supervisor) & Martin Peacock (Other Supervisor)