ArticleScientific reports2015
Combined inhibition of AKT/mTOR and MDM2 enhances Glioblastoma Multiforme cell apoptosis and differentiation of cancer stem cells.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 50 papers.
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.
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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
50 citing papers in PubMed, 93 citations in OpenAlex.
- Drug resistance in glioblastoma: Challenges, mechanisms and therapeutic strategies (Review).Molecular and clinical oncology · 2026Review
- Dysfunction of the Autophagy System and MDM2-p53 Axis Leads to the Accumulation of Amyloidogenic Proteins in Angelman Syndrome Models.International journal of molecular sciences · 2025Article
- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
- Targeted therapy of cancer stem cells: inhibition of mTOR in pre-clinical and clinical research.Cell death & disease · 2024Review
- Discrete Mechanistic Target of Rapamycin Signaling Pathways, Stem Cells, and Therapeutic Targets.Cells · 2024Review
- Combination of Oncolytic Virotherapy with Different Antitumor Approaches against Glioblastoma.International journal of molecular sciences · 2024Review
- Role of Luteolin as Potential New Therapeutic Option for Patients with Glioblastoma through Regulation of Sphingolipid Rheostat.International journal of molecular sciences · 2023Article
- Systems Medicine for Precise Targeting of Glioblastoma.Molecular biotechnology · 2023Review
- Interleukin-21 Influences Glioblastoma Course: Biological Mechanisms and Therapeutic Potential.Cells · 2023Review
- MDM2 Inhibition in the Treatment of Glioblastoma: From Concept to Clinical Investigation.Biomedicines · 2023Review
- E3 ubiquitin ligases in cancer stem cells: key regulators of cancer hallmarks and novel therapeutic opportunities.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- Article
- Wnt and PI3K/Akt/mTOR Survival Pathways as Therapeutic Targets in Glioblastoma.International journal of molecular sciences · 2022Review
- It's Getting Complicated-A Fresh Look at p53-MDM2-ARF Triangle in Tumorigenesis and Cancer Therapy.Frontiers in cell and developmental biology · 2022Review
- Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?Cellular & molecular biology letters · 2021Review
- The Bumpy Road towards mTOR Inhibition in Glioblastoma: Quo Vadis?Biomedicines · 2021Article
- Characterization and Anticancer Activity of Biosynthesized Au/Cellulose Nanocomposite fromPolymers · 2021Article
- mTOR-Rictor-EGFR axis in oncogenesis and diagnosis of glioblastoma multiforme.Molecular biology reports · 2021Review
- Review
- MDM2/X Inhibitors as Radiosensitizers for Glioblastoma Targeted Therapy.Frontiers in oncology · 2021Review
Corrections and comments
- Retracted
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The poor prognosis of Glioblastoma Multiforme (GBM) is due to a high resistance to conventional treatments and to the presence of a subpopulation of glioma stem cells (GSCs). Combination therapies targeting survival/self-renewal signals of GBM and GSCs are emerging as useful tools to improve GBM treatment. In this context, the hyperactivated AKT/mammalian target of the rapamycin (AKT/mTOR) and the inhibited wild-type p53 appear to be good candidates. Herein, the interaction between these pathways was investigated, using the novel AKT/mTOR inhibitor FC85 and ISA27, which re-activates p53 functionality by blocking its endogenous inhibitor murine double minute 2 homologue (MDM2). In GBM cells, FC85 efficiently inhibited AKT/mTOR signalling and reactivated p53 functionality, triggering cellular apoptosis. The combined therapy with ISA27 produced a synergic effect on the inhibition of cell viability and on the reactivation of p53 pathway. Most importantly, FC85 and ISA27 blocked proliferation and promoted the differentiation of GSCs. The simultaneous use of these compounds significantly enhanced GSC differentiation/apoptosis. These findings suggest that FC85 actively enhances the downstream p53 signalling and that a combination strategy aimed at inhibiting the AKT/mTOR pathway and re-activating p53 signalling is potentially effective in GBM and in GSCs.
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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.