> 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-016.md).

# BRE 016

## Electric Fields, Cytokinesis, and Late-Stage Cancer Cell Division

**Clinical Focus:** Cancer Cell Models\
**Common Focus:** Why Cancer Cells May Be Vulnerable While Splitting Into Two Cells

## Source

Berkelmann, L., Bader, A., Meshksar, S., et al. (2019).

*Tumour-treating fields (TTFields): Investigations on the mechanism of action by electromagnetic exposure of cells in telophase/cytokinesis.*

*Scientific Reports, 9, 7362.*

## BRS Score

**BRS:** 8.2 / 10\
**STEMD:** S9 / T7 / E8 / M10 / D7\
**External Evidence Level:** Moderate experimental mechanism evidence

## Score Interpretation

BRE-016 receives a strong BRS because it provides experimental mechanism evidence focused on telophase and cytokinesis, the late stages of cell division. Its strongest value is mechanistic because it helps explain why the physical shape of a dividing cell may increase vulnerability to TTFields.

## Entry Summary

BRE-016 asks a specific question:

**Why might cancer cells be especially vulnerable to electric fields when they are nearly finished dividing?**

This study examined TTFields exposure during telophase and cytokinesis.

Telophase and cytokinesis are late stages of cell division. During this time, one cell is separating into two cells. The middle region between the forming daughter cells becomes narrow and structurally stressed.

BREXAtlas identifies BRE-016 as an important late-mitosis mechanism entry because it connects TTFields response to:

* cell shape
* field concentration
* cytokinetic furrow stress
* division timing
* structural mitotic instability

## What BREXAtlas Found

BREXAtlas found that BRE-016 supports the idea that electric-field effects may become stronger when the cell’s geometry creates a vulnerable point during division.

The extracted mechanism chain is:

TTFields\
↓\
Cytokinetic furrow stress\
↓\
Field concentration effects\
↓\
Structural mitotic instability\
↓\
Failed division / mitotic stress

This makes BRE-016 a key entry for understanding why TTFields may be most disruptive during late mitosis.

## Questions This BRE Helps Answer

### What is cytokinesis?

Cytokinesis is the stage when one cell physically splits into two new cells.

In simple language, this is the “pinching apart” stage of cell division.

**What BREXAtlas found:**\
BRE-016 supports that TTFields may create stress at the cytokinetic furrow, the narrow region where the cell is splitting.

### Why does cell shape matter?

During cytokinesis, the cell is not shaped like a normal round or flat cell. It becomes constricted in the middle.

That shape may concentrate electric-field effects.

**What BREXAtlas found:**\
BRE-016 supports that exposure geometry, cell shape, and division state are relevant to TTFields response.

### Are TTFields effects timing-dependent?

**What BREXAtlas found:**\
Yes. This entry supports the importance of late mitotic and cytokinetic vulnerability.

This means the same cell may not be equally vulnerable at every moment. The dividing state of the cell matters.

## Study Classification

| Study Type                     | Classification                                                   |
| ------------------------------ | ---------------------------------------------------------------- |
| Study Type                     | Experimental electromagnetic exposure / TTFields mechanism study |
| Division Stage Focus           | Telophase / cytokinesis                                          |
| Direct Electric-Field Evidence | Yes                                                              |
| Direct Mechanism Evidence      | Yes                                                              |
| Frequency Index Suitability    | Pending detailed quantitative extraction                         |
| Mechanism Index Suitability    | Yes                                                              |
| Pattern Tracker Suitability    | Yes                                                              |

## Mechanisms

### MEC-020: Dielectrophoretic Force Effects

TTFields may exert physical forces on polar or charged cellular components during division.

### MEC-022: Cytokinetic Furrow Destabilization

The cytokinetic furrow may become a point of structural weakness under TTFields exposure.

### MEC-025: Field-Strength / Directionality Dependence

The effect may depend on field geometry, field direction, and how the dividing cell is oriented.

### MEC-052: Late Mitotic Vulnerability

Cancer cells may be especially vulnerable during telophase and cytokinesis.

### MEC-053: Field Concentration at the Furrow

The narrow geometry of the dividing cell may concentrate electric-field effects near the furrow.

## Discovery

### DISC-008: Cytokinetic Vulnerability Window

BRE-016 supports the discovery that cancer cells may have a vulnerable window during late mitosis, especially during cytokinesis.

This does not replace earlier TTFields mechanisms.

It refines them.

BRE-014 emphasized spindle and chromosome disruption.

BRE-015 emphasized septin and mitotic exit disruption.

BRE-016 emphasizes geometry, furrow stress, and late-stage division vulnerability.

## Connections to Other BRE Entries

### Connected to BRE-014

BRE-014 showed that TTFields can disrupt mitotic spindle organization and chromosome segregation.

BRE-016 adds that late-stage cell shape and cytokinetic geometry may intensify vulnerability.

**Connection:** both support structural mitotic failure.

### Connected to BRE-015

BRE-015 showed septin mislocalization and cytokinetic destabilization.

BRE-016 strengthens that pathway by focusing directly on the furrow and late cytokinesis.

**Connection:** both support cytokinetic instability.

### Connected to BRE-001

BRE-001 introduced the core idea that alternating electric fields can reduce cancer-cell proliferation.

BRE-016 helps explain why that may happen during a specific phase of cell division.

### Connected to BRE-002

BRE-002 focused on frequency optimization.

BRE-016 suggests response may depend not only on frequency, but also on timing, cell geometry, and field direction.

### Connected to BRE-004

BRE-004 observed mitotic disruption and reduced clonogenicity in pancreatic cancer models.

BRE-016 provides a deeper structural explanation for why dividing cells may fail under TTFields exposure.

## Research Gaps Identified

* **RG-077: Division-Stage Timing Gap**\
  More research is needed to determine exactly when cells are most vulnerable to TTFields during mitosis.
* **RG-078: Geometry-Frequency Gap**\
  Unknown whether cell shape and orientation alter optimal frequency response.
* **RG-079: Field Direction Gap**\
  More work is needed to determine how field direction and tumor architecture affect TTFields efficacy.
* **RG-080: Normal Cell Cytokinesis Gap**\
  More studies are needed comparing cytokinetic vulnerability in cancer cells versus normal dividing cells.
* **RG-081: Structural Convergence Gap**\
  Future research should determine how furrow stress interacts with spindle disruption, septin mislocalization, chromosome missegregation, and mitotic catastrophe.

## Why This Entry Matters

For researchers, BRE-016 explains why TTFields may be especially powerful during a narrow window of cell division.

For patients and families, the key idea is simple:

Cancer cells are vulnerable when they are trying to split into two cells. This study suggests electric fields may exploit that vulnerable moment.

BRE-016 does not prove all cancers respond the same way. It does show that timing and cell shape may be important parts of electric-field cancer response.

## Entry Conclusion

BRE-016 strengthens the structural mechanism pathway of the BREXAtlas Encyclopedia.

BRE-014 showed spindle and chromosome disruption.

BRE-015 showed septin and mitotic exit disruption.

BRE-016 shows that the final splitting stage of cell division may be especially vulnerable because of cell shape, furrow stress, and field concentration.

The central question emerging from this entry is:

**Can TTFields be optimized by understanding when and where a dividing cancer cell becomes physically vulnerable?**

For BREXAtlas, BRE-016 is a key entry because it helps connect electric-field response to the geometry and timing of cancer-cell division.


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