ArticleNeuro-oncology advances
Combination MEK and mTOR inhibitor therapy is active in models of glioblastoma.
Article in Neuro-oncology advances. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
30 citing papers in PubMed, 38 citations in OpenAlex.
- Additive effect of Ruta graveolens bioactive phytoconstituents and cisplatin through PKC/MEK/ERK pathway in glioblastoma.Molecular therapy. Oncology · 2026Article
- Combined inhibition of MEK and FOXO1 synergistically suppresses MDA-MB-231 cell proliferation with reduced LOXL4.Journal of clinical biochemistry and nutrition · 2026Article
- Neurofibromatosis Type 1 Tumor Involving the Anterosuperior Mediastinum With a Rare c.147C>G Germline Mutation: A Case Report.Clinical case reports · 2026Article
- MEK inhibitors for neurofibromatosis type 1-associated central and peripheral nervous system tumors.Neuro-oncology advances · 2026Review
- The ERK MAPK pathway in mesenchymal glioblastoma: tumorigenesis, microenvironmental reprogramming, and the therapeutic promise of RAS(ON) multi-selective inhibition.Frontiers in molecular neuroscience · 2026Review
- Neurofibromatosis Type 1 and the Search for Effective Tumor Therapies Using High-Throughput Drug Screening.Current oncology (Toronto, Ont.) · 2025Review
- Tumor heterogeneity underlies clinical outcome and MEK inhibitor response in somatic NF1-mutant glioblastoma.JCI insight · 2025Article
- MEK Inhibition in Glioblastoma: Current Perspectives and Future Directions.International journal of molecular sciences · 2025Review
- Synthesis and Biological Evaluation of MEK/mTOR Multifunctional Inhibitors as Novel Anticancer Agents.Journal of medicinal chemistry · 2025Article
- It's all downstream from here: RTK/Raf/MEK/ERK pathway resistance mechanisms in glioblastoma.Journal of neuro-oncology · 2025Review
- Molecular characterization of gliosarcoma reveals prognostic biomarkers and clinical parallels with glioblastoma.Journal of neuro-oncology · 2025Article
- Effects of combination therapy of a CDK4/6 and MEK inhibitor in diffuse midline glioma preclinical models.PloS one · 2025Article
- NF1 expression profiling in IDH-wildtype glioblastoma: genomic associations and survival outcomes.Acta neuropathologica communications · 2024Article
- Practical immunomodulatory landscape of glioblastoma multiforme (GBM) therapy.Journal of the Egyptian National Cancer Institute · 2024Review
- MEK Inhibition Enhances the Antitumor Effect of Radiotherapy in NF1-Deficient Glioblastoma.Molecular cancer therapeutics · 2024Article
- The complex molecular epileptogenesis landscape of glioblastoma.Cell reports. Medicine · 2024Article
- Rebound growth of BRAF mutant pediatric glioma cells after MAPKi withdrawal is associated with MAPK reactivation and secretion of microglia-recruiting cytokines.Journal of neuro-oncology · 2024Article
- Unveiling Novel Avenues in mTOR-Targeted Therapeutics: Advancements in Glioblastoma Treatment.International journal of molecular sciences · 2023Review
- ERK Signaling Pathway Is Constitutively Active in NT2D1 Non-Seminoma Cells and Its Inhibition Impairs Basal and HGF-Activated Cell Proliferation.Biomedicines · 2023Article
- mTOR Inhibition Is Effective against Growth, Survival and Migration, but Not against Microglia Activation in Preclinical Glioma Models.International journal of molecular sciences · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRAS effector signaling pathways such as PI3K/mTOR and ERK are frequently dysregulated in glioblastoma. While small molecule targeted therapies against these pathways have appeared promising in preclinical studies, they have been disappointing in clinical trials due to toxicity and de novo and adaptive resistance. To identify predictors of glioblastoma sensitivity to dual pathway inhibition with mTORC1/2 and MEK inhibitors, we tested these agents, alone and in combination, in a cohort of genomically characterized glioblastoma cell lines.
methodsSeven genomically characterized, patient-derived glioblastoma neurosphere cell lines were evaluated for their sensitivity to the dual mTORC1/2 kinase inhibitor sapanisertib (MLN0128, TAK-228) alone or in combination with the MEK1/2 inhibitor trametinib (GSK1120212), using assessment of proliferation and evaluation of the downstream signaling consequences of these inhibitors.
resultsSapanisertib inhibited cell growth in neurosphere lines, but induced apoptosis only in a subset of lines, and did not completely inhibit downstream mTOR signaling via ribosomal protein S6 (RPS6). Growth sensitivity to MEK inhibitor monotherapy was observed in a subset of lines defined by loss of NF1, was predicted by an ERK-dependent expression signature, and was associated with effective phospho-RPS6 inhibition. In these lines, combined MEK/mTOR treatment further inhibited growth and induced apoptosis. Combined MEK and mTOR inhibition also led to modest antiproliferative effects in lines with intact NF1 and insensitivity to MEK inhibitor monotherapy.
conclusionsThese data demonstrate that combined MEK/mTOR inhibition is synergistic in glioblastoma cell lines and may be more potent in NF1-deficient glioblastoma.
Indexed as
Identifiers
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.