Abstract

Abstract Tumor-treating fields (TTFields) are low amplitude alternating electric fields which are supposed to exert anti-tumor effects by targeting dividing tumor cells while sparing cells in the brain not undergoing cell division. Although this novel therapeutic approach has shown encouraging results in phase III trials in glioblastoma, its biological effects on tumor cells have only been poorly understood. Here, we investigated the effects of TTFields on glioma cells in vitro using the inovitroTM system that allows the application of TTFields to cell cultures. Exposure to TTFields potently induce autophagy and necroptosis and interfere with the migration and invasion of long-term glioma cell lines, but also of glioma-initiating. The combination of TTFields with irradiation or temozolomide (TMZ) reduced viability and clonogenic survival in an additive or synergistic manner. Further studies suggest that the O6-methyl-guanine DNA methyltransferase (MGMT) status does not influence the efficacy of TTFields and TMZ-resistant glioma cells remain responsive to TTFields application, thus making TTFields particularly attractive for the majority of glioblastoma patients with tumors that are unlikely to benefit from TMZ treatment. In summary, these findings demonstrate that the application of TTFields may interfere with various biological key properties of glioma cells and may allow for a more detailed clinical evaluation of TTFields beyond the clinical data available so far. Citation Format: Manuela Silginer, Michael Weller, Roger Stupp, Patrick Roth. Tumor-treating fields (TTFields) interfere with biological key properties of glioma cells in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1504. doi:10.1158/1538-7445.AM2017-1504

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