> 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-015.md).
# BRE 015
## Electric Fields, Septins, and Abnormal Cancer Cell Division
**Clinical Focus:** Cancer Cell Models\
**Common Focus:** How Electric Fields May Disrupt the Structures Cancer Cells Need to Divide
## Source
Gera, N., Yang, A., Holtzman, T. S., Lee, S. X., Wong, E. T., et al. (2015).
*Tumor Treating Fields Perturb the Localization of Septins and Cause Aberrant Mitotic Exit.*
PLOS ONE, 10(5), e0125269.
***
## BRS Score
**BRS:** 8.2 / 10\
**STEMD:** S9 / T7 / E8 / M10 / D7\
**External Evidence Level:** Moderate experimental mechanism evidence
## Score Interpretation
BRE-015 receives a strong BRS because it provides direct experimental TTFields mechanism evidence. Its strongest value is mechanistic: it identifies septin mislocalization, cytokinetic disruption, abnormal mitotic exit, and reduced tumor-cell viability as part of the TTFields response pathway.
***
## Entry Summary
BRE-015 asks a focused question:
Can Tumor Treating Fields disrupt the structures cancer cells use to finish dividing?
This study found that TTFields altered septin localization and contributed to abnormal mitotic exit.
Septins are structural proteins that help organize the cell during division. They are especially important near the stage when one cell separates into two.
In simple language:
Cancer cells need internal scaffolding to divide correctly. BRE-015 suggests TTFields can disturb part of that scaffolding.
***
## What BREXAtlas Found
BREXAtlas identifies BRE-015 as a structural mitosis entry.
The study supports this mechanism chain:
TTFields\
↓\
Septin mislocalization\
↓\
Cytokinetic disruption\
↓\
Aberrant mitotic exit\
↓\
Reduced tumor-cell viability
This makes BRE-015 one of the clearest mechanism entries showing how TTFields may destabilize cancer-cell division at a structural level.
***
## Questions This BRE Helps Answer
What are septins, and why do they matter?
Septins are proteins that help cells organize their shape and division process.
During cell division, the cell must separate into two daughter cells. Septins help coordinate this process.
What BREXAtlas found:\
BRE-015 supports that TTFields can disturb septin localization, which may make cancer-cell division unstable.
Is TTFields only disrupting chromosomes?
What BREXAtlas found:\
No.
BRE-014 focused on mitotic spindle disruption and chromosome missegregation.
BRE-015 adds another structural layer: septin mislocalization and cytokinetic instability.
Together, these entries suggest TTFields may disrupt more than one part of the division process.
What is aberrant mitotic exit?
Aberrant mitotic exit means a cell leaves the division process incorrectly.
Instead of dividing cleanly, the cell may exit mitosis in a damaged, unstable, or nonviable state.
What BREXAtlas found:\
BRE-015 supports that TTFields can contribute to abnormal mitotic exit and reduced tumor-cell viability.
***
## Study Classification
| Category | Classification |
| ------------------------------------- | ------------------------------------------------ |
| Study Type | Experimental TTFields mechanism study |
| Tissue / Model Focus | Cancer cell models and TTFields exposure systems |
| Direct Electric-Field Evidence | Yes |
| Direct Cancer-Cell Mechanism Evidence | Yes |
| Frequency Index Suitability | Pending detailed quantitative extraction |
| Mechanism Index Suitability | Yes |
| Pattern Tracker Suitability | Yes |
***
## Mechanisms
* **MEC-016: Septin Mislocalization**\
TTFields altered septin localization, disrupting the normal organization of structural proteins during division.
* **MEC-022: Cytokinetic Furrow Destabilization**\
The cell’s division site may become unstable, making successful separation more difficult.
* **MEC-051: Abnormal Mitotic Exit**\
Cancer cells may leave mitosis incorrectly after TTFields exposure.
* **MEC-050: Structural Mitotic Stress**\
BRE-015 reinforces structural mitotic stress as a recurring TTFields mechanism.
***
## Discovery
**DISC-006: Mitotic Structural Collapse Network**
BRE-015 supports the same discovery network as BRE-014.
The shared pattern is that TTFields may create a chain of structural failures during cancer-cell division.
BRE-014 emphasized spindle disruption and chromosome missegregation.
BRE-015 emphasizes septin disruption and abnormal mitotic exit.
Together, they strengthen the mitotic structural collapse model.
***
## Connections to Other BRE Entries
### Connected to BRE-014
BRE-014 showed that alternating electric fields can disrupt mitotic spindle organization, interfere with chromosome segregation, and promote mitotic catastrophe.
BRE-015 extends that mechanism by showing disruption of septin localization and cytokinetic stability.
Connection: both entries support structural failure during cancer-cell division.
***
### Connected to BRE-001
BRE-001 established early evidence that alternating electric fields can reduce cancer-cell proliferation.
BRE-015 helps explain one structural reason why proliferation may decrease.
***
### Connected to BRE-002
BRE-002 focused on identifying optimal inhibitory frequencies.
BRE-015 reinforces why frequency optimization matters: if fields act on specific physical structures, treatment parameters may affect how strongly those structures are disrupted.
***
### Connected to BRE-004
BRE-004 reported reduced clonogenicity and mitotic disruption in pancreatic cancer models.
BRE-015 provides a deeper structural mechanism that may help explain mitotic instability across cancer models.
***
### Connected to BRE-003
BRE-003 focused on DNA repair after radiation.
BRE-015 focuses on cell-division structure.
Together, they suggest TTFields may affect both damage-repair pathways and physical division machinery.
***
## Research Gaps Identified
* **RG-072: Quantitative Parameter Gap**\
Detailed frequency, field intensity, exposure duration, and cell-line-specific response extraction remains needed.
* **RG-073: Septin Specificity Gap**\
More research is needed to determine which septin family members are most affected by TTFields.
* **RG-074: Cross-Cancer Septin Gap**\
Unknown whether septin mislocalization occurs consistently across cancer types.
* **RG-075: Normal Cell Comparison Gap**\
More work is needed to compare septin disruption in cancer cells versus normal dividing cells.
* **RG-076: Structural Cascade Gap**\
Future studies should determine how septin disruption interacts with spindle disruption, chromosome missegregation, and mitotic catastrophe.
***
## Why This Entry Matters
For researchers, BRE-015 adds a specific structural mechanism to the TTFields evidence base.
For patients and families, the main idea is simple:
Cancer cells need to divide correctly to keep growing. This study suggests TTFields may disturb the structures cancer cells need to complete that division.
BRE-015 does not prove that every cancer responds the same way. It does show that TTFields can affect important division machinery inside cancer cells.
***
## Entry Conclusion
BRE-015 strengthens the mechanism pathway introduced by earlier TTFields studies.
BRE-014 showed disruption of the mitotic spindle and chromosomes.
BRE-015 shows disruption of septins and mitotic exit.
The central question emerging from this entry is:
Can TTFields weaken cancer by disrupting multiple structural systems required for cell division?
For BREXAtlas, BRE-015 is a key mechanism entry because it helps explain why electric-field effects may converge on the physical collapse of cancer-cell division.
---
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