ArticleNature communications2017
Induction of synthetic lethality in IDH1-mutated gliomas through inhibition of Bcl-xL.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 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.
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.
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Who cites it
89 citing papers in PubMed, 114 citations in OpenAlex.
- Autophagy inhibition sensitizes radiotherapy responses in high-grade mutant IDH1 glioma.Nature communications · 2026Article
- Unbiased CRISPR synthetic lethal screening for genetic vulnerabilities in a succinate dehydrogenase-loss model of paraganglioma.iScience · 2026Article
- BCL-XbioRxiv : the preprint server for biology · 2025Article
- Autophagy Upregulation in Mutant Isocitrate Dehydrogenase 1 (IDH1) Glioma Uncovers a Novel Therapeutic Target.Research square · 2025Article
- Cell death and cancer: Metabolic interconnections.Cell reports · 2025Review
- Advances in Synthetic Lethality in Potential Oncology Therapeutic Approaches.Current topics in medicinal chemistry · 2025Review
- Integrated molecular and functional characterization of the intrinsic apoptotic machinery identifies therapeutic vulnerabilities in glioma.Nature communications · 2024Article
- Therapeutic targeting of senescent cells in the CNS.Nature reviews. Drug discovery · 2024Review
- A cell state-specific metabolic vulnerability to GPX4-dependent ferroptosis in glioblastoma.The EMBO journal · 2024Article
- Zika Virus: A Neurotropic Warrior against High-Grade Gliomas-Unveiling Its Potential for Oncolytic Virotherapy.Viruses · 2024Review
- OGDH and Bcl-xL loss causes synthetic lethality in glioblastoma.JCI insight · 2024Article
- Review
- Advances in synthetic lethality modalities for glioblastoma multiforme.Open medicine (Warsaw, Poland) · 2024Review
- The Tricarboxylic Acid Cycle Metabolites for Cancer: Friend or Enemy.Research (Washington, D.C.) · 2024Review
- An untapped window of opportunity for glioma: targeting therapy-induced senescence prior to recurrence.NPJ precision oncology · 2023Review
- Review
- DNA Methylation and Histone Modification in Low-Grade Gliomas: Current Understanding and Potential Clinical Targets.Cancers · 2023Review
- D-2-Hydroxyglutarate Inhibits Calcineurin Phosphatase Activity to Abolish NF-AT Activation and IL-2 Induction in Stimulated Lymphocytes.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma.Nature communications · 2023Article
- Translational significance of CDKN2A/B homozygous deletion in isocitrate dehydrogenase-mutant astrocytoma.Neuro-oncology · 2023Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Certain gliomas often harbor a mutation in the activity center of IDH1 (R132H), which leads to the production of the oncometabolite 2-R-2-hydroxyglutarate (2-HG). In six model systems, including patient-derived stem cell-like glioblastoma cultures, inhibition of Bcl-xL induces significantly more apoptosis in IDH1-mutated cells than in wild-type IDH1 cells. Anaplastic astrocytoma samples with mutated IDH1 display lower levels of Mcl-1 than IDH1 wild-type tumors and specific knockdown of Mcl-1 broadly sensitizes glioblastoma cells to Bcl-xL inhibition-mediated apoptosis. Addition of 2-HG to glioblastoma cultures recapitulates the effects of the IDH mutation on intrinsic apoptosis, shuts down oxidative phosphorylation and reduces ATP levels in glioblastoma cells. 2-HG-mediated energy depletion activates AMPK (Threonine 172), blunting protein synthesis and mTOR signaling, culminating in a decline of Mcl-1. In an orthotopic glioblastoma xenograft model expressing mutated IDH1, Bcl-xL inhibition leads to long-term survival. These results demonstrate that IDH1-mutated gliomas are particularly vulnerable to Bcl-xL inhibition.
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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.