A metabolic synthetic lethality of PI3K-driven cancer Article Swipe
Vahid Asnafi
,
Guillaume P. Andrieu
,
Mathieu Simonin
,
Aurélie Cabannes‐Hamy
,
Étienne Lengliné
,
Ambroise Marçais
,
Alexandre Théron
,
Grégoire Huré
,
Jérome Doss
,
Marie‐Emilie Dourthe
,
Nicolas Boissel
,
Hervé Dombret
,
Philippe Rousselot
,
Olivier Hermine
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-3700875/v1
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-3700875/v1
The deregulated activation of the PI3 kinase (PI3K) pathway is a hallmark of aggressive tumors with metabolic plasticity, eliciting their adaptation to the microenvironment and resistance to chemotherapy. A significant gap lies between the biological features of PI3K-driven tumors and the specific targeting of their vulnerabilities. Here, we explored the metabolic liabilities of PI3K-altered T-cell acute lymphoblastic leukemia (T-ALL), an aggressive hematological cancer with dismal outcomes. We revealed a metabolic crosstalk linking glutaminolysis and glycolysis driven by PI3K signaling alterations. Pharmaceutical inhibition of mTOR revealed the singular plasticity of PI3K-altered cells toward the mobilization of glutamine as a salvage pathway to ensure their survival. Subsequently, the combination of glutamine degradation and mTOR inhibition demonstrates robust cytotoxicity in PI3K-driven solid and hematological tumors in pre-clinical and clinical settings. We propose a novel therapeutic strategy to circumvent metabolic adaptation and efficiently target PI3K-driven cancer.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-3700875/v1
- https://www.researchsquare.com/article/rs-3700875/latest.pdf
- OA Status
- gold
- References
- 55
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4391693536
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4391693536Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.21203/rs.3.rs-3700875/v1Digital Object Identifier
- Title
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A metabolic synthetic lethality of PI3K-driven cancerWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2024Year of publication
- Publication date
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2024-02-09Full publication date if available
- Authors
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Vahid Asnafi, Guillaume P. Andrieu, Mathieu Simonin, Aurélie Cabannes‐Hamy, Étienne Lengliné, Ambroise Marçais, Alexandre Théron, Grégoire Huré, Jérome Doss, Marie‐Emilie Dourthe, Nicolas Boissel, Hervé Dombret, Philippe Rousselot, Olivier HermineList of authors in order
- Landing page
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https://doi.org/10.21203/rs.3.rs-3700875/v1Publisher landing page
- PDF URL
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https://www.researchsquare.com/article/rs-3700875/latest.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://www.researchsquare.com/article/rs-3700875/latest.pdfDirect OA link when available
- Concepts
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Synthetic lethality, Lethality, Chemistry, PI3K/AKT/mTOR pathway, Cancer research, Cancer, Computational biology, Biology, Biochemistry, Medicine, Internal medicine, Toxicology, DNA repair, Signal transduction, DNATop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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55Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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