N‐Acetyl‐L‐Cysteine (NAC ) Blunts Axitinib‐Related Adverse Effects in Preclinical Models of Glioblastoma
Article Swipe
Alessia Formato
,
Maria Salbini
,
Elisa Orecchini
,
Manuela Pellegrini
,
Mariachiara Buccarelli
,
Lucia Ricci‐Vitiani
,
Stefano Giannetti
,
Roberto Pallini
,
Quintino Giorgio D’Alessandris
,
Liverana Lauretti
,
Maurizio Martini
,
Valentina De Falco
,
Andrea Levi
,
Maria Laura Falchetti
,
Maria Patrizia Mongiardi
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1002/cam4.70279
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1002/cam4.70279
Objective Axitinib is a tyrosine kinase inhibitor characterized by a strong affinity for Vascular Endothelial Growth Factor Receptors (VEGFRs). It was approved in 2012 by Food and Drug Administration and European Medicines Agency as a second line treatment for advanced renal cell carcinoma and is currently under evaluation in clinical trial for the treatment of other cancers. Glioblastoma IDH‐wild type (GBM) is a highly malignant brain tumor characterized by diffusely infiltrative growth pattern and by a prominent neo‐angiogenesis. In GBM, axitinib has demonstrated a limited effectiveness as a monotherapy, while it was recently shown to significantly improve its efficacy in combination treatments. In preclinical models, axitinib has been reported to trigger cellular senescence both in tumor as well as in normal cells, through a mechanism involving intracellular reactive oxygen species (ROS) accumulation and activation of Ataxia Telangiectasia Mutated kinase (ATM). Limiting axitinib‐dependent ROS increase by antioxidants prevents senescence specifically in normal cells, without affecting tumor cells. Methods We used brain tumor xenografts obtained by engrafting Glioma Stem Cells (GSCs) into the brain of immunocompromised mice, to investigate the hypothesis that the antioxidant molecule N‐Acetyl‐L‐Cysteine (NAC) might be used to reduce senescence‐associated adverse effects of axitinib treatment without altering its anti‐tumor activity. Results We demonstrate that the use of the antioxidant molecule N‐Acetyl‐Cysteine (NAC) in combination with axitinib stabilizes tumor microvessels in GBM tumor orthotopic xenografts, eventually resulting in vessel normalization, and protects liver vasculature from axitinib‐dependent toxicity. Conclusion Overall, we found that NAC co‐treatment allows vessel normalization in brain tumor vessels and exerts a protective effect on liver vasculature, therefore minimizing axitinib‐dependent toxicity.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/cam4.70279
- OA Status
- gold
- Cited By
- 2
- References
- 39
- Related Works
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- OpenAlex ID
- https://openalex.org/W4403214759
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4403214759Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1002/cam4.70279Digital Object Identifier
- Title
-
N‐Acetyl‐L‐Cysteine (
NAC ) Blunts Axitinib‐Related Adverse Effects in Preclinical Models of GlioblastomaWork title - Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-10-01Full publication date if available
- Authors
-
Alessia Formato, Maria Salbini, Elisa Orecchini, Manuela Pellegrini, Mariachiara Buccarelli, Lucia Ricci‐Vitiani, Stefano Giannetti, Roberto Pallini, Quintino Giorgio D’Alessandris, Liverana Lauretti, Maurizio Martini, Valentina De Falco, Andrea Levi, Maria Laura Falchetti, Maria Patrizia MongiardiList of authors in order
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https://doi.org/10.1002/cam4.70279Publisher landing page
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://doi.org/10.1002/cam4.70279Direct OA link when available
- Concepts
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Axitinib, Cancer research, Pharmacology, Medicine, Reactive oxygen species, Angiogenesis, Chemistry, Biochemistry, Sorafenib, Hepatocellular carcinomaTop concepts (fields/topics) attached by OpenAlex
- Cited by
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2Total citation count in OpenAlex
- Citations by year (recent)
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2025: 2Per-year citation counts (last 5 years)
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39Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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