An Evidence-Based Review of Alternating Electric Fields Therapy for Malignant Gliomas
Open accessAbstract
Tumor treating fields (TTFields) represent a novel treatment modality for cancer that utilizes alternating electric fields at an intermediate frequency of 200 kHz. At this specific frequency, TTFields have been shown to penetrate into the head from the surface of the scalp. Computational modeling also showed that the fields are distributed inhomogeneously within the supratentorial regions of the brain, and they tend to become intensified near the ventricles [ 1 •]. At the cellular level, the electromagnetic energy perturbs proteins that have large dipole moments. Cells treated with TTFields exhibited a variety of abnormalities indicative of mitotic catastrophe and aberrant mitotic exit, including cells in polyploidy prophase, rosettes, multi-spindled metaphase, single-spindled metaphase, and asymmetric anaphase [ 2 ]. Indeed, cells exhibit violent membrane blebbing as they enter anaphase and attempt to divide. This results in aberrant mitotic exit and subsequent cell death [ 3 ••]. Some of the proteins that are critical for the proper progression through mitosis have sufficiently high dipole moments to suggest that they may be targets of TTFields, including the mitotic septin complex and the α/β-tubulin monomeric subunit of tubulin. Septins constitute a family of GTP-binding proteins and septin 2, 6, and 7 oligomerize into a heterotrimer with an extremely large dipole moment of 2711 Debyes [ 4 ]. Importantly, this septin complex is required for functions that are necessary for the later stages of cell division. Septin 2, 6, and 7 heterotrimers rapidly polymerize and structurally organize within the cytokinetic furrow as cells exit metaphase. Once it is recruited, it then organizes contractile elements within the cytokinetic furrow above the equatorial cleavage plane by binding to F-actin filaments and spatially regulates myosin activation. RNAi-directed depletion of septin subunits of the heterotrimer results in mitotic catastrophe similar to that seen when cells attempt to divide in the presence of TTFields [ 5 ]. We have shown that TTFields disrupt the ability of septins to re-localize to the cytokinetic furrow and reduce the accumulation of F-actin [ 3 ••]. Therefore, TTFields affect tumor cells by interfering with their ability to complete mitosis by exerting electromagnetic induction forces that interfere with the function of proteins with high dipole moments [ 2 , 3 ••].
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Dividing cells are affected by TTFields during mitosis.
“Indeed, cellular and pre-clinical studies have demonstrated that dividing cells are affected by TTFields during mitosis [8,37].”
From Permeabilizing Cell Membranes with Electric Fields (2021) · cites this paper as [37]
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- Authors
- Wong, E. T., Lok, E., & Swanson, K. D.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Wong, Eric T
- Venue
- Current Treatment Options in Oncology
- Published
- 2015-07-05
- Volume
- 16
- Issue
- 8
- Pages
- 40-40
- ISSN
- 1527-2729 (ISSN-L)
- 1534-6277
- PMC
- PMC4491358
- OpenAlex
- W2135286003
- Cited by
- 35
- References
- 29
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 7 · 2018: 3 · 2017: 4 · 2016: 5 · 2015: 1
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Current Treatment Options in Oncology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Novocure
- Plexxikon
- 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, AC electric field, high-grade glioma, mitotic catastrophe, tubulin, electromagnetic field effects on cells, cell division, F-actin, cancer cell death, non-invasive cancer treatment, glioblastoma, anaplastic astrocytoma
- MeSH terms
- Brain Neoplasms, Glioma, Humans, Neoplasm Recurrence, Local, Treatment Outcome, Electromagnetic Radiation
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