ArticleJCI insight2024
OGDH and Bcl-xL loss causes synthetic lethality in glioblastoma.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 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
8 citing papers in PubMed, 7 citations in OpenAlex.
- MechAInistic: A Reviewer-Supervised Multi-Agent LLM System for Auditable Mechanistic Drug-Hypothesis Generation.bioRxiv : the preprint server for biology · 2026Article
- Ketogenic diet as a metabolic vehicle enhancing the therapeutic efficacy of mebendazole and devimistat in juvenile syngeneic high-grade glioma.Cell reports. Medicine · 2026Article
- Integrating machine learning and retrospective cohort to explore the effects of AEDs on the prognosis of LGG and identify related molecular targets.BMC pharmacology & toxicology · 2026Article
- Synthetic lethality in cancer therapy: Mechanisms, models and clinical translation for overcoming therapeutic resistance.Clinical and translational medicine · 2026Review
- Targeting the Mitochondria in High-Grade Gliomas.Cancers · 2025Review
- A review of the pathogenesis of mitochondria in breast cancer and progress of targeting mitochondria for breast cancer treatment.Journal of translational medicine · 2025Review
- Differential bioenergetic profile of human glioblastoma following transplantation of myocyte-derived mitochondria.PloS one · 2025Article
- ssMutPA: single-sample mutation-based pathway analysis approach for cancer precision medicine.GigaScience · 2024Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Glioblastoma (GBM) remains an incurable disease, requiring more effective therapies. Through interrogation of publicly available CRISPR and RNAi library screens, we identified the α-ketoglutarate dehydrogenase (OGDH) gene, which encodes an enzyme that is part of the tricarboxylic acid (TCA) cycle, as essential for GBM growth. Moreover, by combining transcriptome and metabolite screening analyses, we discovered that loss of function of OGDH by the clinically validated drug compound CPI-613 was synthetically lethal with Bcl-xL inhibition (genetically and through the clinically validated BH3 mimetic, ABT263) in patient-derived xenografts as well neurosphere GBM cultures. CPI-613-mediated energy deprivation drove an integrated stress response with an upregulation of the BH3-only domain protein, Noxa, in an ATF4-dependent manner, as demonstrated by genetic loss-of-function experiments. Consistently, silencing of Noxa attenuated cell death induced by CPI-613 in model systems of GBM. In patient-derived xenograft models of GBM in mice, the combination treatment of ABT263 and CPI-613 suppressed tumor growth and extended animal survival more potently than each compound on its own. Therefore, combined inhibition of Bcl-xL along with disruption of the TCA cycle might be a treatment strategy for GBM.
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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.