Lenvatinib induces ferroptosis-related changes in osteosarcoma cells involving the p-STAT3/p53/xCT axis
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By
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Chunwang Yang
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Yulong Ma
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Wenxiang Shen
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Xiaozhong Ma
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Xiang Liu
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Shaowen Du
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Kaishan Ye
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May 29, 2026
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Clinical Scorecard: Lenvatinib Triggers Ferroptosis-Associated Modifications in Osteosarcoma Cells via the p-STAT3/p53/xCT Pathway
At a Glance
| Category | Detail |
|---|
| Condition | |
| Key Mechanisms | |
| Target Population | Pediatric and adolescent patients with refractory or recurrent osteosarcoma. |
| Care Setting | |
Key Highlights
- Lenvatinib inhibits proliferation of osteosarcoma cells in a concentration-dependent manner.
- Induces ferroptosis characterized by mitochondrial alterations and increased intracellular Fe2+.
- Increases p53 expression and decreases xCT expression.
- Inhibition of STAT3 phosphorylation is associated with lenvatinib treatment.
- Ferrostatin-1 reverses lenvatinib-induced ferroptosis-related changes.
- Potential for chemoresistance and adverse reactions to treatment.
Guideline-Based Recommendations
Diagnosis
Management
Monitoring & Follow-up
- Monitor for changes in cell viability and ferroptosis markers, including intracellular Fe2+ and lipid peroxidation levels.
Risks
Patient & Prescribing Data
Lenvatinib may enhance ferroptosis, impacting tumor cell behavior by increasing cell death.
Clinical Best Practices
- Consider combination therapies such as immunotherapy or other targeted agents to address chemoresistance.
- Monitor mitochondrial changes and ferroptosis markers during treatment.
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