gms | German Medical Science

72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

06.06. - 09.06.2021

Tumor Treating Fields (TTFields) application to cancerous cell lines elevates membrane permeability

Anwendung von Tumor Treating Fields (TTFields) bei Tumorzelllinien erhöht die Membranpermeabilität

Meeting Abstract

  • presenting/speaker Tali Voloshin - NovoCure Ltd., Haifa, Israel
  • Yaara Porat - NovoCure Ltd., Haifa, Israel
  • Alexandra Volodin - NovoCure Ltd., Haifa, Israel
  • Noa Kaynan - NovoCure Ltd., Haifa, Israel
  • Anat Klein-Goldberg - NovoCure Ltd., Haifa, Israel
  • Rom Paz - NovoCure Ltd., Haifa, Israel
  • Boris Brant - NovoCure Ltd., Haifa, Israel
  • Efrat Zemer-Tov - NovoCure Ltd., Haifa, Israel
  • Adi Haber - NovoCure Ltd., Haifa, Israel
  • Moshe Giladi - NovoCure Ltd., Haifa, Israel
  • Adrian Kinzel - NovoCure Ltd., München, Deutschland
  • Uri Weinberg - NovoCure Ltd., Haifa, Israel
  • Yoram Palti - NovoCure Ltd., Haifa, Israel

Deutsche Gesellschaft für Neurochirurgie. 72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie. sine loco [digital], 06.-09.06.2021. Düsseldorf: German Medical Science GMS Publishing House; 2021. DocV295

doi: 10.3205/21dgnc280, urn:nbn:de:0183-21dgnc2806

Published: June 4, 2021

© 2021 Voloshin et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at



Objective: Tumor Treating Fields (TTFields), encompassing intermediate frequency, alternating electric fields, are an anticancer treatment delivered loco-regionally and non-invasively, through transducer arrays placed on the skin, to the tumor region. TTFields therapy has demonstrated efficacy and safety and is CE certified for treatment of patients with glioblastoma (GBM). Recently, TTFields were reported to alter the cellular membrane structure of GBM cells, rendering them more permeable. The objective of this study was to characterize the effect of TTFields treatment on cancer cell permeability and to assess functional significance in combination with other anticancer agents.

Methods: TTFields were applied for 72 h to GBM, uterine sarcoma, and breast adenocarcinoma cell lines across a range of frequencies (50-500 kHz). Cell membrane permeability was assessed by flow cytometry quantification of 7-aminoactinomycin D (7-AAD) intracellular accumulation, and TTFields-elicited cytotoxicity was examined by cell counts. Process kinetics was evaluated by exposing the cells to 7-AAD during the final minutes of treatment versus later time frames following treatment cessation. The potential facilitation of TTFields for enhanced accumulation of anthracycline chemotherapeutics in cancer cells was evaluated in chemotherapy-sensitive and chemotherapy-resistant cells.

Results: TTFields induced increased cellular permeability in all examined cancer cell lines, as evident from elevated 7-AAD accumulation. The highest potency was observed at an optimal frequency that differed from the optimal cytotoxic frequency. TTFields-induced cell membrane permeability was shown to be transient (effective only during delivery), reversible (to normal pretreatment conditions), and able to improve intracellular uptake of chemotherapeutic agents. Moreover, co-application of TTFields allowed accumulation of chemotherapeutic agents in chemotherapy-resistant cancer cells to the same extent as in chemotherapy-sensitive cancer cells.

Conclusion: TTFields treatment increased cancer cell permeability across multiple cancer types, facilitating accumulation of chemotherapeutic drugs, even in chemotherapy-resistant cells. Maximal membrane permeability was obtained at a frequency different from the optimal frequency for inducing cytotoxicity. Of note, enhanced TTFields-induced permeability was transient and reversible, with treatment cessation restoring normal conditions.