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71. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
9. Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

21.06. - 24.06.2020

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Investigation of in vitro response to TTFields and related gene expression in 45 human cell lines

Untersuchung der in vitro TTFields-Response und assoziierter Genexpression in 45 humanen Zelllinien

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  • presenting/speaker Adrian Kinzel - Novocure GmbH, Root, Switzerland
  • Gitit Lavy-Shahaf - Novocure GmbH, Haifa, Israel
  • Moshe Giladi - Novocure GmbH, Haifa, Israel
  • Rosa Schneiderman - Novocure GmbH, Haifa, Israel
  • Karnit Gotlib - Novocure GmbH, Haifa, Israel
  • Einav Zeevi - Novocure GmbH, Haifa, Israel
  • Yaara Porat - Novocure GmbH, Haifa, Israel
  • Mijal Munster - Novocure GmbH, Haifa, Israel
  • Uri Weinberg - Novocure GmbH, Haifa, Israel
  • Eilon Kirson - Novocure GmbH, Haifa, Israel
  • Yoram Palti - Novocure GmbH, Haifa, Israel

Deutsche Gesellschaft für Neurochirurgie. 71. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 9. Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie. sine loco [digital], 21.-24.06.2020. Düsseldorf: German Medical Science GMS Publishing House; 2020. DocV014

doi: 10.3205/20dgnc014, urn:nbn:de:0183-20dgnc0144

Published: June 26, 2020

© 2020 Kinzel et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Objective: Previous investigations showed Tumour Treating Fields (TTFields) to have an inhibitory effect of variable extent in different cancer cell lines. In order to predict TTFields response better in the future, we conducted various analyses of specific properties of cancer cell lines and their individual response pattern.

Methods: After determining their specific optimal frequency, 45 cancer cell lines of diverse human cancer types were treated for 72 h with TTFields with equal nominal intensity of 1.7 V/cm. Cytotoxicity and clonogenic potential was assessed, respectively, and further analysis was conducted with the help of Cancer Cell Line Encyclopedia (CCLE) database. This included functional exploration of mutated or differentially expressed genes related to TTFields response, and contrasting assessment of TTFields sensitivity based on pharmacological profiling (CCLE).

Results: Cytotoxicity and clonogenicity presented very variably between cell lines with up to 86 % reduction in cell count and up to 88 % reduction in colony number, respectively, both with an average of around 50 %. Mutation and gene expression analyses showed pathways relevant in oxidative stress, migration, hypoxia, and DNA damage repair response to be differentially upregulated. We further found cells with a greater TTFields response to be more sensitive to lapatinib, PHA-665752, and PLX-4720.

Conclusion: Our large-scale investigation of TTFields response in various cancer cell lines demonstrated this therapy's broad effectiveness and established every cell line’s optimal treatment frequency. We found first evidence for synergistic effects of TTFields with therapeutic agents that need further investigation in pharmacological profiling studies, in addition to the discovered response-related mutations.