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Carfilzomib Induces Cardiotoxicity by Blocking Autophagic Flux Through the cGAS-STING Signaling Pathway
Shizhong Liu1,2, Xianghong Hou1,3, Daiqianhui Li1,2
1The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University Medical College, Shihezi 832002, China.
Biomolecules
|June 26, 2026
Summary
Carfilzomib (CFZ) causes heart damage by disrupting cellular waste removal (autophagy) via the cGAS-STING pathway. Targeting STING may reduce this cardiotoxicity in multiple myeloma patients.
Area of Science:
- Cardiology
- Molecular Biology
- Pharmacology
Background:
- Carfilzomib (CFZ) is a proteasome inhibitor for multiple myeloma.
- CFZ-induced cardiotoxicity limits its clinical use, with mechanisms poorly understood.
Purpose of the Study:
- Elucidate pathogenic pathways of CFZ-induced cardiotoxicity.
- Investigate the role of autophagy and cGAS-STING signaling in CFZ cardiotoxicity.
Main Methods:
- In vitro studies using AC16 cardiomyocytes and transcriptomic analysis.
- In vivo studies in mice, including STING inhibitor treatment.
- Assessment of mitochondrial function, apoptosis, and autophagic flux.
Main Results:
- CFZ induced mitochondrial dysfunction and apoptosis in cardiomyocytes.
- CFZ impaired autophagic flux by downregulating SNARE proteins, activating cGAS-STING.
- STING inhibition or knockdown ameliorated CFZ-induced cardiac dysfunction and apoptosis.
Conclusions:
- CFZ cardiotoxicity results from cGAS-STING activation, disrupting autophagy and promoting apoptosis.
- Targeting STING offers a potential strategy to mitigate CFZ-induced cardiotoxicity.
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