Biological activity of tumor-treating fields in preclinical glioma models
Open accessAbstract
Glioblastoma is the most common and aggressive form of intrinsic brain tumor with a very poor prognosis. Thus, novel therapeutic approaches are urgently needed. Tumor-treating fields (TTFields) may represent such a novel treatment option. The aim of this study was to investigate the effects of TTFields on glioma cells, as well as the functional characterization of the underlying mechanisms. Here, we assessed the anti-glioma activity of TTFields in several preclinical models. Applying TTFields resulted in the induction of cell death in a frequency- and intensity-dependent manner in long-term glioma cell lines, as well as glioma-initiating cells. Cell death occurred in the absence of caspase activation, but involved autophagy and necroptosis. Severe alterations in cell cycle progression and aberrant mitotic features, such as poly- and micronucleation, preceded the induction of cell death. Furthermore, exposure to TTFields led to reduced migration and invasion, which are both biological hallmarks of glioma cells. The combination of TTFields with irradiation or the alkylating agent, temozolomide (TMZ), resulted in additive or synergistic effects, and the O 6-methyl-guanine DNA methyltransferase status did not influence the efficacy of TTFields. Importantly, TMZ-resistant glioma cells were responsive to TTFields application, highlighting the clinical potential of this therapeutic approach. In summary, our results indicate that TTFields induce autophagy, as well as necroptosis and hamper the migration and invasiveness of glioma cells. These findings may allow for a more detailed clinical evaluation of TTFields beyond the clinical data available so far.
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TTFields induce autophagy in glioma cell lines.
“A recent study supports this hypothesis by providing evidence that TTFields induce autophagy in glioma cell lines17.”
From AMPK-dependent autophagy upregulation serves as a survival mechanism in response to Tumor Treating Fields (TTFields) (2018) · cites this paper as [17]
Silginer et al. demonstrated that concomitant use of 3-MA during TTFields application results in higher cell viability.
“Interestingly, a recent study by Silginer et al.17 demonstrated that the concomitant use of 3-Methyladenine (3-MA; early-stage inhibitor of autophagy) during TTFields application result in higher cell viability.”
From AMPK-dependent autophagy upregulation serves as a survival mechanism in response to Tumor Treating Fields (TTFields) (2018) · cites this paper as [17]
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- Authors
- Silginer, M., Weller, M., Stupp, R., & Roth, P.
- Affiliations
- University of Zurich (CH)
- Corresponding author
- Roth, Patrick
- Venue
- Cell Death & Disease
- Published
- 2017-04-20
- Volume
- 8
- Issue
- 4
- Pages
- e2753-e2753
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC5477589
- OpenAlex
- W2606398715
- Cited by
- 111
- References
- 33
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 11 · 2023: 14 · 2022: 16 · 2021: 15 · 2020: 16 · 2019: 10 · 2018: 14
- FWCI
- 6.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cell Death and Disease (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Novocure
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Electromagnetic Fields and Biological Effects
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Keywords
- tumor treating fields, glioblastoma, glioma, glioma stem cells, autophagy, necroptosis, caspase-independent cell death, cell cycle arrest, micronucleation, cell migration, tumor invasion, temozolomide resistance, radiosensitization, O6-methylguanine-DNA methyltransferase, combination therapy
- MeSH terms
- Temozolomide, Brain Neoplasms, Cell Cycle, Cell Movement, Cell Survival, Dacarbazine, Glioma, Humans, Neoplasm Invasiveness, DNA Modification Methylases, Apoptosis, Caspases, Tumor Suppressor Proteins, DNA Repair Enzymes, Cell Line, Tumor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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