ArticleNeuro-oncology2010
Dual blocking of mTor and PI3K elicits a prodifferentiation effect on glioblastoma stem-like cells.
Article in Neuro-oncology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
55 citing papers in PubMed, 99 citations in OpenAlex.
- Rapamycin Targets Cancer Stem Cells to Decrease Cisplatin Resistance in a Head and Neck Cancer Mouse Xenograft Model.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2026Article
- Targeting chaperone-mediated autophagy inhibits properties of glioblastoma stem cells and restores anti-tumor immunity.Nature communications · 2025Article
- HDAC Class I Inhibitor Domatinostat Induces Apoptosis Preferentially in Glioma Stem Cells Through p53-Dependent and -Independent Activation of BAX Expression.International journal of molecular sciences · 2025Article
- Unveiling Novel Avenues in mTOR-Targeted Therapeutics: Advancements in Glioblastoma Treatment.International journal of molecular sciences · 2023Review
- Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease.Signal transduction and targeted therapy · 2023Review
- Systems Medicine for Precise Targeting of Glioblastoma.Molecular biotechnology · 2023Review
- Human endogenous retrovirus K contributes to a stem cell niche in glioblastoma.The Journal of clinical investigation · 2023Article
- Metformin with Temozolomide for Newly Diagnosed Glioblastoma: Results of Phase I Study and a Brief Review of Relevant Studies.Cancers · 2022Article
- Inhibition of the Phospholipase Cε-c-Jun N-Terminal Kinase Axis Suppresses Glioma Stem Cell Properties.International journal of molecular sciences · 2022Article
- Identification of vascular cues contributing to cancer cell stemness and function.Angiogenesis · 2022Article
- Occurrence of Total and Proteinase K-Resistant Alpha-Synuclein in Glioblastoma Cells Depends on mTOR Activity.Cancers · 2022Article
- SOD2 Enhancement by Long-Term Inhibition of the PI3K Pathway Confers Multi-Drug Resistance and Enhanced Tumor-Initiating Features in Head and Neck Cancer.International journal of molecular sciences · 2021Article
- Rapamycin Ameliorates Defects in Mitochondrial Fission and Mitophagy in Glioblastoma Cells.International journal of molecular sciences · 2021Article
- Targeting RTK-PI3K-mTOR Axis in Gliomas: An Update.International journal of molecular sciences · 2021Review
- Review
- Combined PI3Kα-mTOR Targeting of Glioma Stem Cells.Scientific reports · 2020Article
- mTOR Modulates Intercellular Signals for Enlargement and Infiltration in Glioblastoma Multiforme.Cancers · 2020Review
- Quantitative Ultrastructural Morphometry and Gene Expression of mTOR-Related Mitochondriogenesis within Glioblastoma Cells.International journal of molecular sciences · 2020Article
- The Autophagy Status of Cancer Stem Cells in Gliobastoma Multiforme: From Cancer Promotion to Therapeutic Strategies.International journal of molecular sciences · 2019Review
- The Akt/mTOR pathway in cancer stem/progenitor cells is a potential therapeutic target for glioblastoma and neuroblastoma.Oncotarget · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastoma, the most intractable cerebral tumor, is highly lethal. Recent studies suggest that cancer stem-like cells (CSLCs) have the capacity to repopulate tumors and mediate radio- and chemoresistance, implying that future therapies may need to turn from the elimination of rapidly dividing, but differentiated, tumor cells to specifically targeting the minority of tumor cells that repopulate the tumor. However, the mechanism by which glioblastoma CSLCs maintain their immature stem-like state or, alternatively, become committed to differentiation is poorly understood. Here, we show that the inactivation of mammalian target of rapamycin (mTor) by the mTor inhibitor rapamycin or knockdown of mTor reduced sphere formation and the expression of neural stem cell (NSC)/progenitor markers in CSLCs of the A172 glioblastoma cell line. Interestingly, combination treatment with rapamycin and LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, not only reduced the expression of NSC/progenitor markers more efficiently than single-agent treatment, but also increased the expression of βIII-tubulin, a neuronal differentiation marker. Consistent with these results, a dual PI3K/mTor inhibitor, NVP-BEZ235, elicited a prodifferentiation effect on A172 CSLCs. Moreover, A172 CSLCs, which were induced to undergo differentiation by pretreatment with NVP-BEZ235, exhibited a significant decrease in their tumorigenicity when transplanted either subcutaneously or intracranially. Importantly, similar results were obtained when patient-derived glioblastoma CSLCs were used. These findings suggest that the PI3K/mTor signaling pathway is critical for the maintenance of glioblastoma CSLC properties, and targeting both mTor and PI3K of CSLCs may be an effective therapeutic strategy in glioblastoma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.