Tumor Treating Fields (TTFields) therapy is an approved modality for the treatment of glioblastoma. These alternating electric fields were shown to exert an inhibitory effect in numerous cancer cell lines with some variability in the response of different cell lines. The goal of the present study is to compare characteristics of cell lines based on their response pattern to TTFields.
Forty one different human cancerous cell lines were treated for 72 hours with TTFields at their optimal frequency with the same nominal intensity (1.7 V/cm). Two response values were quantified. The first cytotoxic response, is considered a short-term quantification of the response. The second clonogenic response, is considered a long-term response to TTFields.
Genomic analysis of 26 cell lines was performed based on the Cancer Cell Line Encyclopedia (CCLE) database. Association of mutated genes, mutations and copy number variations with cell lines response to TTFields was investigated.
TTFields application demonstrated varying degree of cytotoxic effect in all cell lines tested. The inhibitory response to TTFields was found to be distributed around an average of 50% with a cytotoxic effects ranging between 14% and 86% reductions in cell counts, and a clonogenic effect ranging between no effect and 88% reduction in the number of colonies. The “Overall response” was considered as the multiplication of the two values and represents the response both in short-term and long-term effects of TTFields. Lower values of all response quantifications indicate a better
response to TTFields. Cell lines were partitioned to responding and non-responding cell lines according to their “Overall response”.
Response to treatment doesn't seem to be affected by the number of mutations in each of the cell lines, and not by the type of the cancer the cell lines originated from. Mutations in genes that associate with the response to TTFields are enriched in GO terms that include muscle function and the intracellular organelle compartment. Mutation association with response to TTFields revealed mutations in genes related to the cytoskeleton, mitotic spindle, receptors and membrane transporters.
This multi parameter, large scale comparison of cancerous cell line response to TTFields demonstrate the broad effectiveness of TTFields in various cell lines and define the optimal frequency to be applied for each cell line. The data presented in this work, suggest that beside their anti-mitotic properties, TTFields may have effects on other cellular pathways.
Citation Format: Kerem Wainer Katsir, Gitit Lavy Shahaf, Moshe Giladi, Rosa S. Schneiderman, Noa Urman, Karnit Gotlieb, Einav Zeevi, Yaara Porat, Mijal Munster, Adrian Kinzel, Uri Weinberg, Eilon D. Kirson, Yoram Palti. Cancer cell lines meta-analysis according to both short-term and long-term responses to Tumor Treating Fields (TTFields) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2411.