ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Protein Kinase B (PKB/AKT) Protects IDH-Mutated Glioma from Ferroptosis via Nrf2.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 33 citations in OpenAlex.
- Emerging roles of ferroptosis in modulating the immune landscape of glial tumours.Nature cell biology · 2026Review
- Arachidonate lipoxygenase 5 metabolism axis promoting ferroptosis: a potential druggable target for doxorubicin-induced cardiomyopathy.British journal of cancer · 2026Article
- Genetic mutations governing ferroptosis sensitivity and resistance: a precision approach to cancer therapy.Cell death & disease · 2026Review
- Ferritinophagy as a Double-Edged Sword in Cancer: Novel Insights into Therapeutic Targeting of Iron-Driven Ferroptosis.Cell biochemistry and biophysics · 2026Review
- Unlocking glioma vulnerabilities: targeting regulated cell death pathways for innovative therapies.Cell death discovery · 2026Review
- Elevated SLC3A2 Expression Promotes the Progression of Gliomas and Enhances Ferroptosis Resistance through the AKT/NRF2/GPX4 Axis.Cancer research and treatment · 2026Article
- Ferroptosis and metabolic reprogramming in the immunosuppressive microenvironment of glioblastoma: emerging mechanisms and novel strategies.Frontiers in immunology · 2026Review
- Targeting PDGFRA-SHP2 signaling enhances radiotherapy in IDH1-mutant glioma.Neuro-oncology · 2025Article
- Integrative analysis of KEAP1/NFE2L2 alterations across 3600+ tumors reveals an NRF2 expression signature as a prognostic biomarker in cancer.NPJ precision oncology · 2025Article
- mtKO: A dedicated guide RNA library for mitochondria research.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeting LINC00707 by vitamin D3 attenuates nitrogen mustard-caused dermal toxicity through inhibiting ferroptosis.Redox biology · 2025Article
- Targeting IDH1 mutation-driven Nrf2 signaling to suppress malignant behavior in fibrosarcoma cells.Toxicological research · 2025Article
- D-2-hydroxyglutarate impairs DNA repair through epigenetic reprogramming.Nature communications · 2025Article
- Perfluorooctanoic Acid Induces Ferroptosis in Hepatocytes via Oxidative Stress and AKT/GSK3β/β-Catenin Pathway Disruption.ACS omega · 2025Article
- Iron and Cell Death.Advances in experimental medicine and biology · 2025Review
- PI3K Signaling at the Crossroads of Lipid Metabolism and Cancer.Advances in experimental medicine and biology · 2025Review
- Targeting ferroptosis to enhance the efficacy of mesenchymal stem cell-based treatments for intervertebral disc degeneration.International journal of biological sciences · 2025Review
- Ferroptosis in Cancer: Epigenetic Control and Therapeutic Opportunities.Biomolecules · 2024Review
- Ferroptosis in glioma therapy: advancements in sensitizing strategies and the complex tumor-promoting roles.Brain research · 2024Review
- Abrogation of the G2/M checkpoint as a chemosensitization approach for alkylating agents.Neuro-oncology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
purposeMutations of the isocitrate dehydrogenase (IDH) gene are common genetic mutations in human malignancies. Increasing evidence indicates that IDH mutations play critical roles in malignant transformation and progression. However, the therapeutic options for IDH-mutated cancers remain limited. In this study, the investigation of patient cohorts revealed that the PI3K/protein kinase B (AKT) signaling pathways were enhanced in IDH-mutated cancer cells. EXPERIMENTAL
designIn this study, we investigated the gene expression profile in IDH-mutated cells using RNA sequencing after the depletion of AKT. Gene set enrichment analysis (GSEA) and pathway enrichment analysis were used to discover altered molecular pathways due to AKT depletion. We further investigated the therapeutic effect of the AKT inhibitor, ipatasertib (Ipa), combined with temozolomide (TMZ) in cell lines and preclinical animal models.
resultsGSEA and pathway enrichment analysis indicated that the PI3K/AKT pathway significantly correlated with Nrf2-guided gene expression and ferroptosis-related pathways. Mechanistically, AKT suppresses the activity of GSK3β and stabilizes Nrf2. Moreover, inhibition of AKT activity with Ipa synergizes with the genotoxic agent TMZ, leading to overwhelming ferroptotic cell death in IDH-mutated cancer cells. The preclinical animal model confirmed that combining Ipa and TMZ treatment prolonged survival.
conclusionsOur findings highlighted AKT/Nrf2 pathways as a potential synthetic lethality target for IDH-mutated cancers.
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.