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Axitinib and HDAC Inhibitors Interact to Kill Sarcoma Cells
Jane L Roberts1, Laurence Booth2, Andrew Poklepovic3
1Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, United States.
Frontiers in Oncology
|October 4, 2021
Summary
Axitinib combined with HDAC inhibitors show potent anti-sarcoma effects by disrupting key cellular pathways and reducing tumor growth. This combination therapy warrants further investigation for sarcoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Histone deacetylase (HDAC) inhibitors are explored for sarcoma treatment.
- Sarcoma is a complex cancer requiring novel therapeutic strategies.
Purpose of the Study:
- To investigate the synergistic effects of axitinib and HDAC inhibitors in sarcoma.
- To elucidate the molecular mechanisms underlying their anti-sarcoma activity.
Main Methods:
- Cellular assays examining protein phosphorylation and autophagic flux.
- Gene knockdown studies to identify key signaling molecules.
- In vivo studies to assess tumor growth inhibition.
Main Results:
- Axitinib and HDAC inhibitors synergistically kill sarcoma cells by inactivating AKT, mTORC1/2, and enhancing autophagic flux.
- This combination reduces HDAC expression and PD-L1 levels, while increasing MHCA.
- Combined treatment significantly inhibits tumor growth in vivo.
Conclusions:
- Axitinib and HDAC inhibitors demonstrate significant anti-sarcoma activity through combined molecular and cellular effects.
- This combination therapy represents a promising novel approach for sarcoma treatment.
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