ArticleScience translational medicine2017
2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity.
Article in Science translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 322 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.
MicroOrganoSphere Drug Screen to Lead Care (MODEL) Precision Oncology Pilot Trial in Colorectal Cancer (CRC)
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
322 citing papers in PubMed, 556 citations in OpenAlex.
- A Phase II Multicenter Trial of Rucaparib and Nivolumab as Maintenance Therapy in Patients with Advanced Biliary Tract Cancer: BilT-02.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Phase I/II and window-of-opportunity study of pamiparib and metronomic temozolomide for recurrent isocitrate dehydrogenase mutant gliomas.Neuro-oncology · 2026Trial
- Phase 2 trial of veliparib, local irradiation, and temozolomide in patients with newly diagnosed high-grade glioma: a Children's Oncology Group study.Neuro-oncology · 2025Trial
- Trial
- Multicenter Phase II Trial of the PARP Inhibitor Olaparib in RecurrentCancer research communications · 2023Trial
- Clinical Efficacy of Olaparib inJCO precision oncology · 2021Trial
- A randomized phase II trial of veliparib, radiotherapy, and temozolomide in patients with unmethylated MGMT glioblastoma: the VERTU study.Neuro-oncology · 2021Trial
- TET2 loss triggers ssDNA gap accumulation and heightened PARP inhibitor sensitivity.Nature communications · 2026Article
- Article
- Comparing artificial intelligence and physician performance in predicting IDH mutation status in glioma.NPJ digital medicine · 2026Article
- Current and emerging therapies in IDH-mutant glioma.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- LIPT1 loss confers replication stress and PARP inhibitor sensitivity through PrimPol-mediated ssDNA gaps.Science advances · 2026Article
- Selective small molecule targeting of KDM4 as a therapeutic strategy to reduce proliferation of acute myeloid leukaemia.British journal of haematology · 2026Article
- SMARCAL1 is a targetable synthetic lethal therapeutic vulnerability in ATRX-deficient gliomas that use alternative lengthening of telomeres.Neuro-oncology · 2026Article
- Mitochondrial targets in IDH1-mutated cholangiocarcinoma.Hepatology communications · 2026Review
- Clinical application of PARP inhibitors and emerging strategies to overcome resistance: a pan-cancer perspective.Biomarker research · 2026Review
- Exploiting synthetic lethality in epithelial ovarian cancer: multi-dimensional approaches beyond DNA damage repair.Molecular cancer · 2026Review
- Poly ADP Ribose Polymerase Inhibitors Potentiate Proton Therapy End-of-Range Effects by Accelerating Replication Forks and Promoting Transcription Conflict.International journal of radiation oncology, biology, physics · 2026Article
- Epigenetic Regulation of Higher-Order Chromatin Structure (HOCS) and Its Implication in Human Diseases.Cancers · 2026Review
- Metastatic progression of pheochromocytoma and paraganglioma occurs via parallel evolution.NPJ precision oncology · 2026Article
262 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
21 authors at 1 institution in 1 country.
Funding
Abstract
2-Hydroxyglutarate (2HG) exists as two enantiomers, (R)-2HG and (S)-2HG, and both are implicated in tumor progression via their inhibitory effects on α-ketoglutarate (αKG)-dependent dioxygenases. The former is an oncometabolite that is induced by the neomorphic activity conferred by isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations, whereas the latter is produced under pathologic processes such as hypoxia. We report that IDH1/2 mutations induce a homologous recombination (HR) defect that renders tumor cells exquisitely sensitive to poly(adenosine 5'-diphosphate-ribose) polymerase (PARP) inhibitors. This "BRCAness" phenotype of IDH mutant cells can be completely reversed by treatment with small-molecule inhibitors of the mutant IDH1 enzyme, and conversely, it can be entirely recapitulated by treatment with either of the 2HG enantiomers in cells with intact IDH1/2 proteins. We demonstrate mutant IDH1-dependent PARP inhibitor sensitivity in a range of clinically relevant models, including primary patient-derived glioma cells in culture and genetically matched tumor xenografts in vivo. These findings provide the basis for a possible therapeutic strategy exploiting the biological consequences of mutant IDH, rather than attempting to block 2HG production, by targeting the 2HG-dependent HR deficiency with PARP inhibition. Furthermore, our results uncover an unexpected link between oncometabolites, altered DNA repair, and genetic instability.
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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.