ArticleMolecular cell2023
Oncogenic IDH mutations increase heterochromatin-related replication stress without impacting homologous recombination.
Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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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
37 citing papers in PubMed, 41 citations in OpenAlex.
- 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
- Multi-omics profiling reveals homologous recombination repair hyperactivation as a therapeutic vulnerability in neuroendocrine cervical carcinoma.Signal transduction and targeted therapy · 2026Article
- Replication stress in cancer: origins, consequences and therapeutic opportunities.Nature reviews. Cancer · 2026Review
- ERCC6 at the Transcription-Replication Interface: Integration of Transcription-Coupled Repair with Replication Stress Responses.International journal of molecular sciences · 2026Review
- Chromosomal Instability Drives Glioblastoma Heterogeneity and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- 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
- SMARCAL1 is a targetable synthetic lethal therapeutic vulnerability in ATRX-deficient gliomas that use alternative lengthening of telomeres.Neuro-oncology · 2026Article
- PDK4 is critical for metabolic regulation and progesterone production in bovine granulosa cells†.Biology of reproduction · 2026Article
- Prickle4 Drives Microenvironmental Remodeling and Resistance to Parp Inhibition in IDH-Mutant Glioma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PARP inhibitor resistance in IDH1-mutant cancers due to loss of end protection factors, 53BP1 and REV7.NAR cancer · 2025Article
- Nucleoplasmic Lamin A/C controls replication fork restart upon stress by modulating local H3K9me3 and ADP-ribosylation levels.Nature communications · 2025Article
- Targeting the crosstalk of metabolism reprogramming and replication stress: novel strategy to combat cancer.Medical oncology (Northwood, London, England) · 2025Review
- Novel Strategies for Improved Treatment of O6-Methylguanine-DNA Methyltransferase Promoter-Methylated Glioma.Medical research archives · 2025Article
- Mitochondrial metabolism and cancer therapeutic innovation.Signal transduction and targeted therapy · 2025Review
- Deconvoluting clonal and cellular architecture in IDH-mutant acute myeloid leukemia.Cell stem cell · 2025Article
- R-2-hydroxyglutarate-mediated inhibition of KDM4A compromises telomere integrity.Nucleic acids research · 2025Article
- Oligodendroglioma: Advances in Molecular Mechanisms and Immunotherapeutic Strategies.Biomedicines · 2025Review
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16 authors at 3 institutions in 1 country.
Funding
Abstract
Oncogenic mutations in isocitrate dehydrogenases 1 and 2 (IDH1/2) produce 2-hydroxyglutarate (2HG), which inhibits dioxygenases that modulate chromatin dynamics. The effects of 2HG have been reported to sensitize IDH tumors to poly-(ADP-ribose) polymerase (PARP) inhibitors. However, unlike PARP-inhibitor-sensitive BRCA1/2 tumors, which exhibit impaired homologous recombination, IDH-mutant tumors have a silent mutational profile and lack signatures associated with impaired homologous recombination. Instead, 2HG-producing IDH mutations lead to a heterochromatin-dependent slowing of DNA replication accompanied by increased replication stress and DNA double-strand breaks. This replicative stress manifests as replication fork slowing, but the breaks are repaired without a significant increase in mutation burden. Faithful resolution of replicative stress in IDH-mutant cells is dependent on poly-(ADP-ribosylation). Treatment with PARP inhibitors increases DNA replication but results in incomplete DNA repair. These findings demonstrate a role for PARP in the replication of heterochromatin and further validate PARP as a therapeutic target in IDH-mutant tumors.
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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.