ArticleNeuro-oncology2022
PI3K/AKT/mTOR signaling pathway activity in IDH-mutant diffuse glioma and clinical implications.
Article in Neuro-oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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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
45 citing papers in PubMed, 73 citations in OpenAlex.
- Everolimus for Children With Recurrent or Progressive Low-Grade Glioma: Results From the Phase II PNOC001 Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Trial
- Mitochondrial Metabolic Reprogramming in Glioma: Mechanisms of Tumorigenesis and Implications for Clinical Therapy.CNS neuroscience & therapeutics · 2026Review
- Heterogeneity in cancer: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- POFUT1 Serves as an Independent Prognostic Factor and Therapeutic Target by Activating the PI3K/AKT Pathway in Glioma.Brain and behavior · 2026Article
- Clinical and molecular response to vorasidenib in post-transplant patient with IDH2-mutant intrahepatic cholangiocarcinoma.The oncologist · 2026Article
- Inhibition of EIF2S1 expression regulates the PI3K/AKT pathway to mediate apoptosis in glioma cells: an in vitro study.Neurogenetics · 2026Article
- A Genomically Tailored Multiagent Precision Medicine Clinical Trial for Adults with Recurrent Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Nebivolol suppresses glioblastoma progression via dual modulation of mitochondrial metabolism and AKT/mTOR/4EBP1 signaling axis.PLoS genetics · 2026Article
- Multiple patient-derived glioblastoma models reveal synthetic lethality through concurrent PI3K and CDK4/6 inhibition by blocking trans-active cooperation.Neuro-oncology · 2026Article
- Multi-Omics Evidence Based on Spatial Transcriptomics Data Reveals the Therapeutic Value of Copper Death Genes in Glioblastoma.International journal of genomics · 2026Article
- Multiscale Pancancer Analysis Uncovers Intrinsic Imaging and Molecular Characteristics Prominent in Breast Cancer and Glioblastoma.British journal of cancer · 2026Article
- miR-139-5p suppresses hepatocellular carcinoma progression by targeting SMOX to inhibit AKT-mTOR pathway and epithelial-mesenchymal transition.Scientific reports · 2025Article
- The Role of mTOR Signaling in Tumor-Induced Alterations to Neuronal Function in Diffusely Infiltrating Glioma.Biomedicines · 2025Review
- Tumor-related epilepsy in glioma: A multidisciplinary overview.Epilepsia · 2025Review
- Natural compounds as regulators of miRNAs: exploring a new avenue for treating brain cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- SERPINB6 Promotes Epithelial-Mesenchymal Transition via PI3K/AKT/mTOR Signalling Pathway in Glioma.Journal of cellular and molecular medicine · 2025Article
- Impact of SPP1 and HMOX1 Genes in Glioma: Correlations With Oncolytic Virus Infection, Adverse Prognosis and Increased Cell Proliferation.Journal of cellular and molecular medicine · 2025Article
- The role of FAM111B in the malignant progression and molecular regulation of human glioma through the PI3K/Akt pathway.Chinese neurosurgical journal · 2025Article
- The role of SPI1/VSIG4/THBS1 on glioblastoma progression through modulation of the PI3K/AKT pathway.Journal of advanced research · 2025Article
- GSK3 acts as a switch for transcriptional programs in a model of low-grade gliomagenesis.Acta neuropathologica communications · 2025Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
backgroundIDH-mutant diffuse gliomas are heterogeneous, and improved methods for optimal patient therapeutic stratification are needed. PI3K/AKT/mTOR signaling activity can drive disease progression and potential therapeutic inhibitors of the pathway are available. Yet, the prevalence of PI3K/AKT/mTOR signaling pathway activity in IDH-mutant glioma is unclear and few robust strategies to assess activity in clinical samples exist.
methodsPI3K/AKT/mTOR signaling pathway activity was evaluated in a retrospective cohort of 132 IDH-mutant diffuse glioma (91 astrocytoma and 41 oligodendroglioma, 1p/19q-codeleted) through quantitative multiplex immunoprofiling using phospho-specific antibodies for PI3K/AKT/mTOR pathway members, PRAS40, RPS6, and 4EBP1, and tumor-specific anti-IDH1 R132H. Expression levels were correlated with genomic evaluation of pathway intrinsic genes and univariate and multivariate Cox proportional hazard regression models were used to evaluate the relationship with outcome.
resultsTumor-specific expression of p-PRAS40, p-RPS6, and p-4EBP1 was common in IDH-mutant diffuse glioma and increased with CNS WHO grade from 2 to 3. Genomic analysis predicted pathway activity in 21.7% (13/60) while protein evaluation identified active PI3K/AKT/mTOR signaling in 56.6% (34/60). Comparison of expression in male versus female patients suggested sexual dimorphism. Of particular interest, when adjusting for clinical prognostic factors, the level of phosphorylation of RPS6 was strongly associated with PFS (P < .005). Phosphorylation levels of both PRAS40 and RPS6 showed an association with PFS in univariate analysis.
conclusionsOur study emphasizes the value of proteomic assessment of signaling pathway activity in tumors as a means to identify relevant oncogenic pathways and potentially as a biomarker for identifying aggressive disease.
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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.