ArticleCell reports2015
Oncometabolite D-2-Hydroxyglutarate Inhibits ALKBH DNA Repair Enzymes and Sensitizes IDH Mutant Cells to Alkylating Agents.
Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06258018 (A Phase I-II Study of Niraparib Plus Temozolomide "One Week on, One Week Off" in Patients With Recurrent Isocitrate Dehydrogenase), which is not on this map. Cited by 125 papers, 1 of them a synthesis that pooled it.
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.
A Phase I-II Study of Niraparib Plus Temozolomide "One Week on, One Week Off" in Patients With Recurrent Isocitrate Dehydrogenase (IDH) Wild Type Glioblastoma and IDH Mutant Gliomas.
Who cites it
125 citing papers in PubMed, 1 synthesis or guideline pooled it, 198 citations in OpenAlex.
- Interplay Between Glucose Metabolism and Chromatin Modifications in Cancer.Frontiers in cell and developmental biology · 2021Pooled it
- The DNA methylome of DDR genes and benefit from RT or TMZ in IDH mutant low-grade glioma treated in EORTC 22033.Acta neuropathologica · 2018Trial
- Resolving challenges in detection and quantification of D-2-hydroxyglutarate and L-2-hydroxyglutarate via LC/MS.Methods (San Diego, Calif.) · 2026Article
- Cholangiocarcinoma:Unveiling the cold tumor microenvironment and strategies for immune rejuvenation.Oncogene · 2026Review
- Article
- Postoperative Anti-NMDA Receptor Encephalitis Following Resection of an Insular Astrocytoma: A Case Report.Brain tumor research and treatment · 2026Article
- E3 ligase LMO7 promotes ALKBH2 ubiquitination to sensitize MGMT-deficient glioblastoma to temozolomide.Cell death & disease · 2026Article
- mPharmaceuticals (Basel, Switzerland) · 2026Review
- Discovery of chirally dependent protein modifications by D- and L-2-hydroxyglutarates.Nature chemistry · 2026Article
- Review
- The crosstalk between epigenetics and metabolism in the malignant cell.Discover oncology · 2026Review
- Review
- The TRiC/CCT Complex at the Crossroads of Metabolism and Hypoxia in GBM: Implications for IDH-Dependent Therapeutic Targeting.International journal of molecular sciences · 2025Review
- Article
- Profiling Inhibitor Scaffolds for the Cancer Target Jumonji-C Domain-Containing Protein 6.ChemMedChem · 2025Article
- Targeting the crosstalk of metabolism reprogramming and replication stress: novel strategy to combat cancer.Medical oncology (Northwood, London, England) · 2025Review
- TCA cycle-derived oncometabolites in cancer and the immune microenvironment.Journal of biomedical science · 2025Review
- Novel Strategies for Improved Treatment of O6-Methylguanine-DNA Methyltransferase Promoter-Methylated Glioma.Medical research archives · 2025Article
- IDH1 Mutation Impacts DNA Repair Through ALKBH2 Rendering Glioblastoma Cells Sensitive to Artesunate.Biomedicines · 2025Article
- D-2-hydroxyglutarate impairs DNA repair through epigenetic reprogramming.Nature communications · 2025Article
65 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Chemotherapy of a combination of DNA alkylating agents, procarbazine and lomustine (CCNU), and a microtubule poison, vincristine, offers a significant benefit to a subset of glioma patients. The benefit of this regimen, known as PCV, was recently linked to IDH mutation that occurs frequently in glioma and produces D-2-hydroxyglutarate (D-2-HG), a competitive inhibitor of α-ketoglutarate (α-KG). We report here that D-2-HG inhibits the α-KG-dependent alkB homolog (ALKBH) DNA repair enzymes. Cells expressing mutant IDH display reduced repair kinetics, accumulate more DNA damages, and are sensitized to alkylating agents. The observed sensitization to alkylating agents requires the catalytic activity of mutant IDH to produce D-2-HG and can be reversed by the deletion of mutant IDH allele or overexpression of ALKBH2 or AKLBH3. Our results suggest that impairment of DNA repair may contribute to tumorigenesis driven by IDH mutations and that alkylating agents may merit exploration for treating IDH-mutated cancer patients.
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.