ArticleNeuro-oncology2021
PARP-mediated PARylation of MGMT is critical to promote repair of temozolomide-induced O6-methylguanine DNA damage in glioblastoma.
Article in Neuro-oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
96 citing papers in PubMed, 138 citations in OpenAlex.
- Phase Ib/II Study of Pamiparib Plus Radiation Therapy and/or Temozolomide in Adult Patients with Treatment-Naïve or Recurrent/Refractory Glioblastoma.Current oncology (Toronto, Ont.) · 2025Trial
- 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
- A multi-site phase I trial of Veliparib with standard radiation and temozolomide in patients with newly diagnosed glioblastoma multiforme (GBM).Journal of neuro-oncology · 2023Trial
- Tumor Treating Fields Enhance Temozolomide-Associated Growth Suppression in Glioblastoma Cells and Patient-Derived Organoids Through Cell-Cycle Blockade, Apoptosis, and SMAD-Associated Signaling.CNS neuroscience & therapeutics · 2026Article
- METTL3 Increases Temozolomide Resistance in MGMT-Negative Glioblastoma by Enhancing CBX5 mRNA Stability in an mCNS neuroscience & therapeutics · 2026Article
- Natural and Synthetic Compounds, Swords for Glioblastoma Therapy: From Tumor to Its Microenvironment.International journal of molecular sciences · 2026Review
- Exosome Secretion Drives Chemo-Resistance of Temozolomide in Glioblastoma.Journal of extracellular biology · 2026Article
- Dual Targeting Strategy: Colchicine and Paclitaxel Combination Against Prostate Cancer Cells Colchicine-Paclitaxel Synergy in Prostate Cancer.Medeniyet medical journal · 2026Article
- PARP inhibitors target cellular energy metabolism: Mechanisms of action and clinical implications.Translational oncology · 2026Review
- Folic Acid-Guided PLGA-Zein Core-Shell Nanoparticles for Co-Delivery of Temozolomide and Ellagic Acid to Overcome PARP-Mediated Chemoresistance in Glioblastoma.Pharmaceutics · 2026Article
- Deciphering the glioblastoma microenvironmental landscape with multi-modal radiogenomics to guide prognosis and personalized therapy.Journal of translational medicine · 2026Article
- Multi-omics clustering combined with multiple machine learning to identify epigenetic features in low-grade glioma patients.Translational cancer research · 2026Article
- Overcoming blood-brain barrier and chemoresistance in glioblastoma by Angiopep-2-modified NK cell-derived extracellular vesicles for targeted delivery of temozolomide.Journal of nanobiotechnology · 2026Article
- SCD1 and SCD5 modulate PARP-dependent DNA repair via fatty acid desaturation in glioblastoma.Cell reports · 2026Article
- miR-181d coordinates homologous recombination and anti-tumor immune responses in glioblastoma.iScience · 2026Article
- Leveraging proteomics and machine learning for mechanism and biomarker discovery on glioma progression and transformation: from LGG to GBM.Human genomics · 2026Article
- Metal-based nanomaterials achieve tumor treatment strategies by overcoming the blood-brain barrier of glioma and responding to the tumor microenvironment.Materials today. Bio · 2026Review
- MGMT upregulation mediates Temozolomide resistance conferred USP5 dependency.Scientific reports · 2026Article
- ACYP2 Induces Temozolomide Resistance in Glioblastoma by Promoting PARP1-Mediated DNA Damage Repair.Molecular cancer research : MCR · 2026Article
- 20(S)-protopanaxadiol enhances temozolomide responsiveness in MGMT-expressing glioblastoma: Wnt/β-catenin attenuation and MGMT downregulation.Frontiers in medicine · 2026Article
36 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
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundTemozolomide (TMZ) resistance in glioblastoma multiforme (GBM) is mediated by the DNA repair protein O6-methylguanine DNA methyltransferase (MGMT). MGMT promoter methylation (occurs in about 40% of patients) is associated with loss of MGMT expression (MGMT-) that compromises DNA repair, leading to a favorable response to TMZ therapy. The 60% of patients with unmethylated MGMT (MGMT+) GBM experience resistance to TMZ; in these patients, understanding the mechanism of MGMT-mediated repair and modulating MGMT activity may lead to enhanced TMZ activity. Here, we report a novel mode of regulation of MGMT protein activity by poly(ADP-ribose) polymerase (PARP).
methodsMGMT-PARP interaction was detected by co-immunoprecipitation. PARylation of MGMT and PARP was detected by co-immunoprecipitation with anti-PAR antibody. O6-methylguanine (O6-MetG) adducts were quantified by immunofluorescence assay. In vivo studies were conducted in mice to determine the effectiveness of PARP inhibition in sensitizing GBM to TMZ.
resultsWe demonstrated that PARP physically binds with MGMT and PARylates MGMT in response to TMZ treatment. In addition, PARylation of MGMT by PARP is required for MGMT binding to chromatin to enhance the removal of O6-MetG adducts from DNA after TMZ treatment. PARP inhibitors reduced PARP-MGMT binding and MGMT PARylation, silencing MGMT activity to repair O6-MetG. PARP inhibition restored TMZ sensitivity in vivo in MGMT-expressing GBM.
conclusionThis study demonstrated that PARylation of MGMT by PARP is critical for repairing TMZ-induced O6-MetG, and inhibition of PARylation by PARP inhibitor reduces MGMT function rendering sensitization to TMZ, providing a rationale for combining PARP inhibitors to sensitize TMZ in MGMT-unmethylated GBM.
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.