> 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-040.md).
# BRE 040
**TTFields, ROS-Mediated Apoptosis, and Doxorubicin Sensitization in Liposarcoma**
**Clinical Cancer Name:** Liposarcoma\
**Common Cancer Name:** Soft Tissue Sarcoma / Fat-Tissue Cancer
## Source
Lee, W. S., Jang, Y., Cho, A., Kim, Y. B., Bu, Y. H., Yang, S., & Kim, E. H. (2023).
*Effectiveness of Tumor-Treating Fields to Reduce the Proliferation and Migration of Liposarcoma Cell Lines.*
*Experimental and Therapeutic Medicine, 26, 363.*
***
## BRS Score
**BRS:** 8.5 / 10\
**STEMD:** S8 / T8 / E8 / M8 / D9\
**External Evidence Level:** Moderate experimental in-vitro evidence
## Score Interpretation
BRE-040 receives a strong score because it provides direct in-vitro evidence that TTFields reduced proliferation, viability, colony formation, and migration in liposarcoma cell lines. It also shows doxorubicin amplified TTFields effects.
***
## Entry Summary
BRE-040 asks a soft tissue cancer question:
Can TTFields weaken liposarcoma cells and make doxorubicin more effective?
This study tested liposarcoma cell lines SW872 and 94T778 using TTFields at 150 kHz and 1.0 V/cm.
In simple language:
Electric fields slowed liposarcoma cells in the lab. When doxorubicin was added, the response became stronger.
***
## What BREXAtlas Found
BREXAtlas identifies this primary mechanism chain:
TTFields\
↓\
ROS increase\
↓\
Oxidative stress\
↓\
Caspase-3 activation\
↓\
Apoptosis\
↓\
Tumor-cell death
A secondary chain is:
TTFields\
↓\
Migration suppression\
↓\
Reduced invasive potential\
↓\
Reduced tumor spread
The combination chain is:
TTFields\
+\
Doxorubicin\
↓\
Enhanced oxidative stress\
↓\
Enhanced apoptotic signaling\
↓\
Improved tumor suppression
This makes BRE-040 important because it shows TTFields may transfer into soft tissue sarcoma models through ROS-mediated apoptosis and chemotherapy sensitization.
***
## Questions This BRE Helps Answer
What is liposarcoma?
Liposarcoma is a soft tissue sarcoma that begins in fat-related tissue.
What BREXAtlas found:\
BRE-040 studies liposarcoma cell lines SW872 and 94T778.
What frequency was used?
What BREXAtlas found:\
The study used TTFields at 150 kHz and 1.0 V/cm.
Did TTFields affect cancer-cell movement?
What BREXAtlas found:\
Yes. TTFields inhibited migration, which matters because migration is related to cancer spread.
Why does doxorubicin matter?
Doxorubicin is a chemotherapy drug used in several cancer treatment contexts.
What BREXAtlas found:\
Doxorubicin amplified TTFields effects and increased tumor sensitivity in liposarcoma models.
***
## Study Classification
| Category | Classification |
| ---------------------------------- | ------------------------------------ |
| Study Type | Experimental in-vitro TTFields study |
| Tissue Category | Liposarcoma / soft tissue sarcoma |
| Cell Lines | SW872, 94T778 |
| Frequency | 150 kHz |
| Field Strength | 1.0 V/cm |
| Combination Agent | Doxorubicin |
| Direct TTFields Evidence | Yes |
| Direct Combination Evidence | Yes |
| Suitable for Sarcoma Index | Yes |
| Suitable for Frequency Index | Yes |
| Suitable for ROS / Apoptosis Index | Yes |
***
## Mechanisms
**MEC-031: Mitochondrial Electrical Stress**
BRE-040 strengthens existing mitochondrial-electrical ontology through ROS and apoptosis evidence, but it does not directly measure mitochondrial respiration.
**MEC-032: ROS-Electromagnetic Coupling**
TTFields increased ROS production and oxidative stress.
**MEC-050: TTFields Chemotherapy Co-Amplification**
Doxorubicin amplified TTFields effects.
**MEC-094: Liposarcoma Migration Suppression**
TTFields suppressed migration in liposarcoma cell models.
**MEC-095: Soft Tissue Sarcoma TTFields Transferability**
BRE-040 supports TTFields transfer into a soft tissue sarcoma model.
***
## Discoveries
**DISC-020: Electromagnetic Mitochondrial Respiration Disruption**
BRE-040 strengthens ROS-related mitochondrial-electrical ontology but does not directly demonstrate ETC disruption, SDH inhibition, mitochondrial permeability transition, or radical-pair mechanisms.
**DISC-021: Clinical Systems-Level TTFields Integration**
BRE-040 supports the broader TTFields integration pathway by extending application into another tumor type.
**DISC-025: Soft Tissue Sarcoma TTFields Sensitivity**
BREXAtlas identifies this as a tissue-expansion discovery:
Liposarcoma cell models may be sensitive to TTFields at 150 kHz, especially when combined with doxorubicin.
***
## Connections to Other BRE Entries
**Connected to BRE-039**
BRE-039 showed TTFields plus doxorubicin and radiation amplified lung cancer suppression.
BRE-040 shows TTFields plus doxorubicin amplification in liposarcoma.
**Connected to BRE-033 and BRE-034**
BRE-033 and BRE-034 showed TTFields combination amplification with sorafenib in liver cancer.
BRE-040 shows a similar combination-amplification logic with doxorubicin in soft tissue sarcoma.
**Connected to BRE-035**
BRE-035 directly linked electromagnetic exposure with mitochondrial respiration disruption.
BRE-040 strengthens ROS and mitochondrial-electrical ontology but does not directly measure mitochondrial respiration.
**Connected to BRE-020**
BRE-020 synthesized TTFields combination potential with chemotherapy.
BRE-040 provides direct soft tissue sarcoma support for that pathway.
**Connected to BRE-021**
BRE-021 emphasized frequency optimization across tumor types.
BRE-040 contributes a 150 kHz TTFields point for liposarcoma.
***
## Research Gaps Identified
**RG-198: Liposarcoma Frequency Optimization Gap**
More research is needed to determine whether 150 kHz is optimal across liposarcoma subtypes.
**RG-199: Sarcoma Cell-Line Expansion Gap**
More liposarcoma and soft tissue sarcoma models should be tested.
**RG-200: Doxorubicin Sequencing Gap**
Future studies should determine whether TTFields should be applied before, during, or after doxorubicin.
**RG-201: Normal Soft Tissue Safety Gap**
More comparison is needed with normal fat and soft tissue cells.
**RG-202: In-Vivo Translation Gap**
The findings require in-vivo validation and eventually clinical testing.
***
## Scientific Caution
BRE-040 strengthens existing mitochondrial-electrical ontology, but it does not directly demonstrate electron transport chain disruption, SDH inhibition, mitochondrial permeability transition, radical-pair mechanisms, or direct mitochondrial respiration measurements.
***
## Why This Entry Matters
For researchers, BRE-040 matters because it expands TTFields evidence into soft tissue sarcoma.
For patients and families, the simple idea is this:
Liposarcoma cells exposed to electric fields grew less and moved less in the lab. Doxorubicin made the effect stronger.
This is not proof of a clinical treatment yet. It is a strong reason to keep studying TTFields in sarcoma models.
***
## Entry Conclusion
BRE-040 expands BREXAtlas into soft tissue sarcoma.
BRE-039 showed lung cancer combination amplification with doxorubicin and radiation.
BRE-040 shows liposarcoma response to TTFields plus doxorubicin through ROS, caspase-3 activation, apoptosis, and migration suppression.
The central question emerging from this entry is:
Can TTFields be optimized as a chemotherapy-sensitizing strategy for liposarcoma and other soft tissue sarcomas?
For BREXAtlas, BRE-040 is important because it adds sarcoma to the cross-tissue TTFields response map.
---
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