> 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/bre-014.md). # BRE 014 ## Electric Fields, Mitotic Spindle Disruption, and Cancer Cell Division **Clinical Focus:** Cancer Cell Models\ **Common Focus:** How TTFields May Disrupt Cancer Cells While They Divide ## Source Giladi, M., Schneiderman, R. S., Voloshin, T., Porat, Y., Munster, M., Blat, R., Sherbo, S., Bomzon, Z., Urman, N., Itzhaki, A., Cahal, S., Shteingauz, A., Chaudhry, A., Kirson, E. D., Weinberg, U., & Palti, Y. (2015). *Mitotic Spindle Disruption by Alternating Electric Fields Leads to Improper Chromosome Segregation and Mitotic Catastrophe in Cancer Cells.* *Scientific Reports, 5, 18046.* Legacy Repository Note: Some early BREXAtlas files labeled this source as Giladi 2016. The correct publication year is 2015. The 2016 label should only be treated as a legacy retrieval label. *** ## Giladi Source Audit BRE-014 is the *Scientific Reports* mitotic-spindle mechanism paper. It should remain separate from: | BRE | Correct Source | Year | Main Focus | | ------- | --------------------------------: | ------------------ | ---------------------------------------------------------------------------------------- | | BRE-003 | Giladi et al., Radiation Oncology | 2017 | Glioma, radiation, DNA damage repair delay, Rad51, gamma-H2AX, radiosensitization | | BRE-004 | Giladi et al., Pancreatology | 2014 | Pancreatic cancer, 150 kHz, reduced clonogenicity, chemotherapy combinations | | BRE-014 | Giladi et al., Scientific Reports | 2015 / legacy 2016 | Microtubules, mitotic spindle disruption, chromosome missegregation, mitotic catastrophe | Rule: Scientific Reports 5:18046 routes to BRE-014, not BRE-004. *** ## BRS Score | Metric | Value | | ----------------------- | ---------------------------------------- | | BRS | 8.4 / 10 | | STEMD | S9 / T7 / E8 / M10 / D8 | | External Evidence Level | Moderate experimental mechanism evidence | ## Score Interpretation BRE-014 receives a strong BRS because it provides direct experimental TTFields mechanism evidence. Its strongest category is mechanism strength because the study connects alternating electric-field exposure to mitotic spindle disruption, microtubule dynamics, chromosome missegregation, mitotic catastrophe, and reduced tumor-cell proliferation. *** ## Entry Summary BRE-014 asks a core question: How do alternating electric fields disrupt dividing cancer cells? BREXAtlas identifies this study as a core TTFields mechanism entry. The study supports the idea that TTFields can interfere with the internal structures cancer cells rely on during division. In simple language: Cancer cells must divide to grow. During division, they use a structure called the mitotic spindle to separate chromosomes correctly. BRE-014 found that TTFields can disrupt that process, leading to improper chromosome separation, aneuploidy, multinucleation, mitotic catastrophe, and cell death. *** ## What BREXAtlas Found BREXAtlas found that BRE-014 strengthens the anti-mitotic foundation first introduced in BRE-001 and separates the mechanism pathway from the pancreatic-specific evidence in BRE-004. The study supports this chain: TTFields exposure\ ↓\ Microtubule / mitotic spindle disruption\ ↓\ Improper chromosome segregation\ ↓\ Aneuploidy + multinucleation\ ↓\ Mitotic catastrophe\ ↓\ Caspase-mediated apoptosis / reduced clonogenic survival This makes BRE-014 one of the clearest mechanism-anchor entries in Volume I. *** ## Questions This BRE Helps Answer
Why are dividing cancer cells vulnerable to electric fields? Dividing cells are physically reorganizing themselves. Their internal structures are moving, chromosomes are being separated, and the cell is preparing to split. What BREXAtlas found: BRE-014 supports that TTFields can disrupt mitotic spindle organization during this vulnerable process.
Do TTFields affect microtubules? What BREXAtlas found: Yes. BRE-014 reports decreased polymerized tubulin after TTFields exposure and supports microtubule dynamics as a central mechanism.
What is mitotic catastrophe? Mitotic catastrophe is a failure of cell division so severe that the cell cannot complete division normally. What BREXAtlas found: BRE-014 connects TTFields exposure with chromosome missegregation, aneuploidy, multinucleation, and mitotic catastrophe. This helps explain why tumor-cell proliferation and long-term clonogenic survival may be reduced after TTFields exposure.
Does treatment duration matter? What BREXAtlas found: Yes. BRE-014 shows that TTFields efficacy depends on cell doubling time and exposure duration. Longer exposure gives slower-dividing cells more opportunity to pass through mitosis while under TTFields stress.
Is this evidence for all electromagnetic therapies? What BREXAtlas found: No. This study anchors TTFields mechanism evidence and should not be generalized to non-TTFields electromagnetic exposures, Rife-type devices, low-frequency stimulation, or unsupported frequency claims without direct supporting evidence.
*** ## Study Classification | Category | Classification | | -------------------------------------------- | ------------------------------------------------------------------------------------ | | Study Type | Experimental TTFields mechanism study | | Tissue / Model Focus | Cancer cell models exposed to alternating electric fields, plus F98 rat glioma model | | Frequency Evidence | 150 kHz and 200 kHz cell-line-specific TTFields models | | Direct Bioelectric / Electric-Field Evidence | Yes | | Direct Cancer-Cell Mechanism Evidence | Yes | | Suitable for Mechanism Index | Yes | | Suitable for Frequency Index | Yes, where cell-line-specific frequencies are reported | | Suitable for Pattern Tracker | Yes | *** ## Cell Lines and Models | Cell Line / Model | Cancer Context | Frequency | | ----------------- | -------------------------- | --------- | | A2780 | Ovarian cancer | 200 kHz | | A549 | Lung adenocarcinoma | 150 kHz | | AsPC-1 | Pancreatic adenocarcinoma | 150 kHz | | HeLa | Cervical adenocarcinoma | 150 kHz | | MCF-7 | Breast adenocarcinoma | 150 kHz | | MDA-MB-231 | Breast adenocarcinoma | 150 kHz | | MSTO-211H | Mesothelioma | 150 kHz | | NCI-H1299 | NSCLC / lung carcinoma | 150 kHz | | NCI-H2052 | Mesothelioma | 200 kHz | | U-87 MG | Glioblastoma / astrocytoma | 200 kHz | | U-118 MG | Glioblastoma / astrocytoma | 200 kHz | | F98 | Rat glioma model | 200 kHz | *** ## Mechanisms * **MEC-001: Mitotic Disruption**\ TTFields interfere with the process cancer cells use to divide. * **MEC-017: Mitotic Catastrophe**\ Electric-field exposure may push dividing cancer cells into failed division. * **MEC-021: Chromosome Missegregation**\ The study observed abnormal chromosome segregation after TTFields exposure. * **MEC-050: Structural Mitotic Stress**\ BREXAtlas classifies this as a structural stress mechanism because TTFields appear to disrupt the physical organization of mitosis. *** ## Discovery **DISC-006: Mitotic Structural Collapse Network** BRE-014 supports the discovery that TTFields may create a cascade of structural failure during cancer-cell division. This discovery connects spindle disruption, chromosome errors, mitotic catastrophe, and reduced proliferation into one mechanism pathway. *** ## Connections to Other BRE Entries | Connected Entry | Relationship | | --------------- | ---------------------------------------------------------------------------------------------------------------- | | BRE-001 | Foundational TTFields efficacy and frequency-specific response | | BRE-003 | Separate Giladi 2017 glioma radiation / DNA repair delay entry | | BRE-004 | Separate Giladi 2014 pancreatic cancer TTFields entry | | BRE-005 | TTFields-induced cell death may connect upstream mitotic catastrophe to downstream immune activation | | BRE-012 | Systems theory framework helps explain why mitotic disruption can be interpreted as a system-level vulnerability | *** ## Research Gaps | Gap ID | Gap Name | | ------ | ------------------------------------- | | RG-092 | Giladi Source Numbering Gap | | RG-093 | Microtubule Direct-Interaction Gap | | RG-094 | p53 Response Gap | | RG-095 | Cell Fate Divergence Gap | | RG-096 | Doubling-Time Translation Gap | | RG-097 | Duration Optimization Gap | | RG-098 | Mitotic Catastrophe Threshold Gap | | RG-099 | Cross-Cancer Mechanism Validation Gap | *** ## BREXAtlas Tags * TTFields * Mitotic Spindle Disruption * Microtubule Dynamics * Tubulin Polymerization * Chromosome Missegregation * Aneuploidy * Multinucleation * Mitotic Catastrophe * Caspase-Mediated Apoptosis * Treatment Duration * Cell Doubling Time * Clonogenic Survival * Mechanism Anchor --- # Agent Instructions This documentation is published with GitBook. GitBook is the documentation platform designed so that both humans and AI agents can read, navigate, and reason over technical content effectively. Learn more at gitbook.com. ## Querying This Documentation If you need additional information that is not directly available in this page, you can query the documentation dynamically by asking a question. Perform an HTTP GET request on the current page URL with the `ask` query parameter, and the optional `goal` query parameter: ``` GET https://www.brexatlas.org/bre-001/bre-014.md?ask=&goal= ``` `ask` is the immediate question: it should be specific, self-contained, and written in natural language. `goal` is optional and describes the broader end goal you are ultimately trying to accomplish on behalf of the user. GitBook uses it to tailor the answer towards what is most useful for that goal. The response will contain a direct answer to the question and relevant excerpts and sources from the documentation. Use this mechanism when the answer is not explicitly present in the current page, you need clarification or additional context, or you want to retrieve related documentation sections.