The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
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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“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]
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“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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Self-citationMGMT Gene Silencing and Benefit from Temozolomide in Glioblastoma
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Self-citationGlioma stem cells promote radioresistance by preferential activation of the DNA damage response
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Biomechanics and biophysics of cancer cells☆
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Self-citationAlternating electric fields arrest cell proliferation in animal tumor models and human brain tumors
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Tumour treating fields therapy for glioblastoma: current advances and future directions
Rominiyi, O., Vanderlinden, A., Clenton, S. J., Bridgewater, C. H., Al-Tamimi, Y., & Collis, S. J. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-01136-5 · Cited by 342
Pseudolaric acid B triggers ferroptosis in glioma cells via activation of Nox4 and inhibition of xCT
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Toms, S. A., Kim, C., Nicholas, G. A., & Ram, Z. (2018) · Journal of Neuro-Oncology · doi:10.1007/s11060-018-03057-z · Cited by 188
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Tumor treating fields increases membrane permeability in glioblastoma cells
Chang, E., Patel, C. B., Pohling, C., Young, C., Song, J., Flores, T. A., Zeng, Y., Joubert, L.-M., Arami, H., Natarajan, A., et al. (2018) · Cell Death Discovery · doi:10.1038/s41420-018-0130-x · Cited by 137
Metadata
- 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 › Oncology › 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
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