ArticleNature communications2018
A novel enhancer regulates MGMT expression and promotes temozolomide resistance in glioblastoma.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
156 citing papers in PubMed, 2 syntheses or guidelines pooled it, 280 citations in OpenAlex.
- The dual role of circHIPK3 in cancer and its implications for multiple drugs resistance: a systematic review and computational approach.Frontiers in oncology · 2025Pooled it
- Clinical Efficacy of Temozolomide and Its Predictors in Aggressive Pituitary Tumors and Pituitary Carcinomas: A Systematic Review and Meta-Analysis.Frontiers in neurology · 2021Pooled it
- METTL3 Increases Temozolomide Resistance in MGMT-Negative Glioblastoma by Enhancing CBX5 mRNA Stability in an mCNS neuroscience & therapeutics · 2026Article
- Construction Strategies, Microenvironmental Modelling and Precision-Therapy Applications of Glioma Organoid Models.Cancers · 2026Review
- Divergent Roles of Canonical and Non-Canonical Mismatch Repair in Regulating Temozolomide Sensitivity in Glioblastoma.International journal of molecular sciences · 2026Review
- Tetrahedral framework nucleic acids: Nanokeys unlocking a new era of precision biomedicine.Journal of advanced research · 2026Review
- MAGMAS Inhibition Enhances Temozolomide Efficacy in Chemotherapy-Resistant Glioblastoma Models.Cancer research communications · 2026Article
- Modeling blood-brain barrier-glioblastoma interactions: implications for chemoresistance and therapeutic targeting.Fluids and barriers of the CNS · 2026Review
- Cinobufotalin reduces glioblastoma resistance to temozolomide by inhibiting the CCL5-mediated PI3K/Akt/mTOR signaling pathway.Translational cancer research · 2026Article
- Deciphering the STAT3-PXN positive feedback loop in GBM, IDH-wildtype: transcriptional regulation and inhibition of YB-1 ubiquitination.Cell death discovery · 2026Article
- RFC4 drives temozolomide resistance in glioblastoma by activating STK38-BECN1-dependent autophagy.Nature communications · 2026Article
- Targeting BRD4-A Promising Therapeutic Option for Glioblastoma?International journal of molecular sciences · 2026Review
- Article
- 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
- The role of USP19 in human diseases: from molecular function to clinical relevance.Frontiers in immunology · 2026Review
- Leveraging External Data for Testing Experimental Therapies with Biomarker Interactions in Randomized Clinical Trials.Biometrika · 2026Article
- Enhancer-mediated NR2F2 recruitment activates BGN to promote tumor growth and shape tumor microenvironment in papillary thyroid cancer.Theranostics · 2026Article
- Tumor-derived apolipoprotein E confers resistance to temozolomide in pancreatic neuroendocrine tumors.Cell death & disease · 2025Article
- Design, synthesis, and evaluation of novel pinane-based thiazolidione derivatives with anti-glioblastoma activity.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Elevated expression and secretion of TGF-α contribute to Temozolomide resistance in human glioblastoma cells.Cancer cell international · 2025Article
96 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
Temozolomide (TMZ) was used for the treatment of glioblastoma (GBM) for over a decade, but its treatment benefits are limited by acquired resistance, a process that remains incompletely understood. Here we report that an enhancer, located between the promoters of marker of proliferation Ki67 (MKI67) and O6-methylguanine-DNA-methyltransferase (MGMT) genes, is activated in TMZ-resistant patient-derived xenograft (PDX) lines and recurrent tumor samples. Activation of the enhancer correlates with increased MGMT expression, a major known mechanism for TMZ resistance. We show that forced activation of the enhancer in cell lines with low MGMT expression results in elevated MGMT expression. Deletion of this enhancer in cell lines with high MGMT expression leads to a dramatic reduction of MGMT and a lesser extent of Ki67 expression, increased TMZ sensitivity, and impaired proliferation. Together, these studies uncover a mechanism that regulates MGMT expression, confers TMZ resistance, and potentially regulates tumor proliferation.
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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.