> For the complete documentation index, see [llms.txt](https://www.brexatlas.org/llms.txt). Markdown versions of documentation pages are available by appending `.md` to page URLs; this page is available as [Markdown](https://www.brexatlas.org/bre-001.md). # BRE 001 ## Alternating Electric Fields and Brain Cancer Response **Clinical Cancer Name:** Glioblastoma / Glioma\ **Common Cancer Name:** Brain Cancer ## Source Kirson, E. D., Dbalý, V., Tovaryš, F., Vymazal, J., Soustiel, J. F., Itzhaki, A., Mordechovich, D., Steinberg-Shapira, S., Gurvich, Z., Schneiderman, R., Wasserman, Y., Salzberg, M., Ryffel, B., Goldsher, D., Dekel, E., & Palti, Y. (2007). Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors. *Proceedings of the National Academy of Sciences of the United States of America, 104*(24), 10152–10157. *** ## BRS Score | Field | Value | | ----------------------- | -------------------------------------------------------- | | BRS | 7.6 / 10 | | STEMD | S8 / T8 / E7 / M8 / D7 | | External Evidence Level | Foundational experimental and clinical TTFields evidence | ### STEMD Dimension | STEMD Dimension | Score | Reason | | --------------------- | ----: | ------------------------------------------------------------------------------------------ | | S — Specificity | 8 | Specific cancer focus, glioma/glioblastoma, with F-98, U-87, and U-118 models. | | T — Translation | 8 | Includes animal tumor models and human brain tumor relevance. | | E — Evidence Strength | 7 | Foundational study; frequency verified, but some intensity/duration values remain pending. | | M — Mechanism Clarity | 8 | Clear mitotic disruption mechanism. | | D — Discovery Value | 7 | Establishes early frequency-response and TTFields foundation. | ### Score Interpretation BRE-001 receives a strong foundational score because it establishes TTFields as a cancer-response intervention in glioma/glioblastoma models using 200 kHz and showing reduced proliferation and tumor growth inhibition. It remains slightly limited because field intensity, exposure duration, and response percentage require further verification. *** ## Entry Summary This foundational study asked whether carefully controlled alternating electric fields could slow or stop cancer cell growth without using traditional chemotherapy, radiation, or surgery. The study focused mainly on brain cancer, especially glioma and glioblastoma, while also testing other cancer cell types. BREXAtlas identifies this source as one of the earliest major studies showing that cancer cells may have measurable electric-field response patterns. In simple terms, this study suggests that some cancer cells may be vulnerable during the moment they divide. Tumor Treating Fields, or TTFields, appear to interfere with that division process. Instead of poisoning the cell chemically, the electric field disrupts the physical process cancer cells need in order to multiply. *** ## Question This BRE Helps Answer
Can electric fields slow cancer growth? What BREXAtlas found:\ Yes. In this study, alternating electric fields reduced cancer cell proliferation and inhibited tumor growth in experimental models. The strongest evidence in this entry relates to brain cancer models, especially glioma and glioblastoma. What still needs more research:\ This does not mean all cancers respond the same way. More studies are needed to determine which cancers, cell lines, and treatment settings respond best.
Is the response frequency-specific? What BREXAtlas found:\ Yes. Different cancer cell lines showed different optimal frequencies. Observed frequency patterns included: | Cancer Type | Cell Line | Observed Optimal Frequency | | --------------------- | ---------- | -------------------------- | | Melanoma | B16F1 | 100 kHz | | Breast cancer | MDA-MB-231 | 150 kHz | | Brain cancer / glioma | F-98 | 200 kHz | | Brain cancer / glioma | U-87 | 200 kHz | | Brain cancer / glioma | U-118 | 200 kHz | This is important because it suggests cancer response may not be one-size-fits-all. A brain cancer cell line may respond differently than a breast cancer or melanoma cell line.
What mechanism did the study support? What BREXAtlas found:\ The main mechanism was disruption of mitosis, which is the process cells use to divide. The study supports three related mechanisms: 1. Mitotic spindle interference\ The electric field may interfere with structures cancer cells need to separate correctly during division. 2. Dielectrophoretic disruption\ Electric forces may disturb charged or polar parts of the cell during division. 3. Cleavage furrow disruption\ As the cell pinches into two new cells, the electric field may physically disrupt that process. In everyday language: the field appears to attack cancer cells at one of their most vulnerable moments — when they are trying to split and multiply.
Did stronger or better-positioned fields matter? What BREXAtlas found:\ Yes. Field direction mattered. The study found stronger tumor-growth inhibition when fields were applied from more than one direction. In rat glioma models: | Field Direction Setup | Tumor Growth Inhibition | | --------------------- | ----------------------- | | One direction | 19.8% reduction | | Two directions | 42.6% reduction | | Three directions | 53.4% reduction | This suggests that electric-field treatment may depend not only on frequency, but also on how the field is delivered.
Was normal tissue safety addressed? What BREXAtlas found:\ The study reported limited systemic toxicity. The primary treatment-related side effect was mild to moderate skin irritation beneath electrodes. What still needs more research:\ This entry supports a favorable early safety profile, but it does not fully answer how every normal tissue responds across every possible frequency, intensity, and exposure duration.
*** ## Cell Lines Cataloged in This Entry ### Primary Brain Cancer Cell Lines * F-98 rat glioma * U-87 human glioma * U-118 human glioma ### Additional Cell Lines Mentioned * B16F1 mouse melanoma * MDA-MB-231 human breast cancer * H1299 human non-small-cell lung cancer *** ## Treatment Parameters | Parameter | BREXAtlas Extraction | | ------------------------- | ---------------------------------- | | Treatment Type | Tumor Treating Fields | | Common Term | Alternating electric-field therapy | | Frequency Range Highlight | 100–200 kHz depending on cell line | | Brain Cancer Frequency | 200 kHz | | Field Intensity | 1–2 V/cm | | Cell Culture Exposure | 24 hours | | Animal Model Exposure | 6 days | | Human GBM Exposure | Average 18 hours per day | *** ## What BREXAtlas Found BREXAtlas classifies BRE-001 as a foundational evidence entry because it supports four major findings: 1. Cancer cells can respond to alternating electric fields. 2. Different cancer cell lines may require different frequencies. 3. Electric fields appear to interfere with cancer cell division. 4. Treatment delivery matters, including direction, duration, and intensity. This entry provides early evidence that bioelectric cancer response can be cataloged by cell line, tissue type, frequency, and mechanism. *** ## Public Source Validation Public scientific indexing and literature databases identify this study as a foundational Tumor Treating Fields publication. Public summaries of TTFields describe the therapy as low-intensity, intermediate-frequency electric fields that disrupt cancer cell division, which aligns with BREXAtlas interpretation. BREXAtlas does not add private or unsupported claims here. Its added value is organization: it places the study into a structured encyclopedia format that connects frequency, cancer type, cell line, mechanism, and research gaps. *** ## Connections to Other BRE Entries ### Connected to BRE-002 Connection: BRE-001 establishes early TTFields evidence. BRE-002 should be read next when comparing whether later studies confirm, refine, or challenge the frequency-specific response pattern. ### Connected to Future Breast Cancer Entries Connection: BRE-001 includes MDA-MB-231, a breast cancer cell line. Future breast cancer entries should compare whether 150 kHz remains supported across breast cancer models. ### Connected to Future Lung Cancer Entries Connection: BRE-001 includes H1299, a non-small-cell lung cancer cell line. Future lung cancer entries should examine whether TTFields frequency response differs from brain and breast cancer patterns. ### Connected to Future Melanoma Entries Connection: BRE-001 includes B16F1 melanoma response at 100 kHz. This creates an early comparison point for lower-frequency response patterns. *** ## Research Gaps Identified ### RG-001: Frequency Prediction Gap Can optimal frequency be predicted from cell size, tissue type, or electrical properties? ### RG-002: Cross-Cancer Comparison Gap Do different cancers follow a consistent frequency pattern, or does each cell line need individual testing? ### RG-003: Normal Tissue Protection Gap What is the highest useful treatment exposure that disrupts cancer cells without harming normal tissue? ### RG-004: Mechanism Expansion Gap Is mitotic disruption the only major mechanism, or are other bioelectric pathways involved? ### RG-005: Delivery Optimization Gap How should frequency, field intensity, direction, and treatment duration be combined for best effect? *** ## Why This Entry Matters For scientists, BRE-001 helps frame electric-field cancer therapy as something that can be measured, compared, and organized. For patients and families, the key takeaway is simpler: this study helped establish that cancer cells may have electrical vulnerabilities, especially while dividing. BRE-001 does not prove that every cancer can be treated with electric fields. It does show that the question is scientifically serious and worth organizing across many cancer types. *** ## Entry Conclusion BRE-001 is the opening entry of the BREXAtlas Encyclopedia because it introduces the central idea behind the entire project: Cancer response to electric fields can be studied systematically. This study shows that frequency, cell type, field direction, and treatment duration matter. It also gives BREXAtlas its first major organizing principle: bioelectric cancer response should be mapped, compared, and updated as evidence grows. 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