ArticleInternational journal of molecular sciences2019
Second Generation mTOR Inhibitors as a Double-Edged Sword in Malignant Glioma Treatment.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Systematic Review of Molecular Targeted Therapies for Adult-Type Diffuse Glioma: An Analysis of Clinical and Laboratory Studies.International journal of molecular sciences · 2023Pooled it
- Targeting glioblastoma mitochondrial metabolism with S-Gboxin induces cytotoxicity under conditions of the tumor microenvironment.Cell death discovery · 2026Article
- Glioma‑associated microglia and macrophages as a potential target for mTOR inhibition in glioblastoma.Molecular medicine reports · 2025Article
- Mesenchymal Properties of Glioma Cell Lines.Bulletin of experimental biology and medicine · 2024Article
- An AMP-activated protein kinase-PGC-1α axis mediates metabolic plasticity in glioblastoma.Clinical and translational medicine · 2024Article
- Article
- Superoxide dismutase 1 mediates adaptation to the tumor microenvironment of glioma cells via mammalian target of rapamycin complex 1.Cell death discovery · 2024Article
- Article
- mTOR Inhibition Is Effective against Growth, Survival and Migration, but Not against Microglia Activation in Preclinical Glioma Models.International journal of molecular sciences · 2023Article
- Article
- Clinically relevant glioblastoma patient-derived xenograft models to guide drug development and identify molecular signatures.Frontiers in oncology · 2023Article
- Inhibition of mTOR signaling protects human glioma cells from hypoxia-induced cell death in an autophagy-independent manner.Cell death discovery · 2022Article
- A Preliminary Study of the Effect of Quercetin on Cytotoxicity, Apoptosis, and Stress Responses in Glioblastoma Cell Lines.International journal of molecular sciences · 2022Article
- The Bumpy Road towards mTOR Inhibition in Glioblastoma: Quo Vadis?Biomedicines · 2021Article
- PI3K Pathway Inhibition with NVP-BEZ235 Hinders Glycolytic Metabolism in Glioblastoma Multiforme Cells.Cells · 2021Article
- Targeting RTK-PI3K-mTOR Axis in Gliomas: An Update.International journal of molecular sciences · 2021Review
- Torin2 inhibits the EGFR-TKI resistant Non-Small Lung Cancer cell proliferation through negative feedback regulation of Akt/mTOR signaling.Journal of Cancer · 2020Article
- Rapamycin-Loaded Lipid Nanocapsules Induce Selective Inhibition of the mTORC1-Signaling Pathway in Glioblastoma Cells.Frontiers in bioengineering and biotechnology · 2020Article
- mTORC1 as a Regulator of Mitochondrial Functions and a Therapeutic Target in Cancer.Frontiers in oncology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Glioblastomas (GBs) frequently display activation of the epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR). mTOR exists as part of two multiprotein complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2). In GBs, mTORC1 inhibitors such as rapamycin have performed poorly in clinical trials, and in vitro protect GB cells from nutrient and oxygen deprivation. Next generation ATP-competitive mTOR inhibitors with affinity for both mTOR complexes have been developed, but data exploring their effects on GB metabolism are scarce. In this study, we compared the ATP-competitive mTORC1/2 inhibitors torin2, INK-128 and NVP-Bez235 to the allosteric mTORC1 inhibitor rapamycin under conditions that mimic the glioma microenvironment. In addition to inhibiting mTORC2 signaling, INK-128 and NVP-Bez235 more effectively blocked mTORC1 signaling and prompted a stronger cell growth inhibition, partly by inducing cell cycle arrest. However, under hypoxic and nutrient-poor conditions mTORC1/2 inhibitors displayed even stronger cytoprotective effects than rapamycin by reducing oxygen and glucose consumption. Thus, therapies that arrest proliferation and inhibit anabolic metabolism must be expected to improve energy homeostasis of tumor cells. These results mandate caution when treating physiologically or therapeutically induced hypoxic GBs with mTOR inhibitors.
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What OpenQuestion holds
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.