ArticleOncogene2020
EGFRvIII upregulates DNA mismatch repair resulting in increased temozolomide sensitivity of MGMT promoter methylated glioblastoma.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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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
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- The Prognostic Significance of Epidermal Growth Factor Receptor Amplification and Epidermal Growth Factor Receptor Variant III Mutation in Glioblastoma: A Systematic Review and Meta-Analysis with Implications for Targeted Therapy.International journal of molecular sciences · 2025Pooled it
- Systems biology of Wnt signaling in glioma chemotherapy resistance: Integrating multi-omics mechanisms and emerging therapeutic vulnerabilities (Review).Oncology letters · 2026Review
- Radiotherapy resistance in glioblastoma: Mechanistic insights and novel therapeutic approaches (Review).International journal of oncology · 2026Review
- Modeling blood-brain barrier-glioblastoma interactions: implications for chemoresistance and therapeutic targeting.Fluids and barriers of the CNS · 2026Review
- Tumor antigen only (TAO) vaccine platforms for glioblastoma therapeutics: a systematic review of evidence from clinical trials.EClinicalMedicine · 2026Review
- Transcriptional condensates enrich phosphorylated PRMT2 to stimulate H3R8me2a deposition and hypoxic response in glioblastoma.Science China. Life sciences · 2026Article
- Defining treatment-resistant brain cancer: Genetic screening to identify oncogene-driven immunomodulation and therapy resistance.Cancer gene therapy · 2026Review
- Drug resistant glioblastoma stem cells exhibit enriched stemness signatures and share extracellular matrix overexpression.BMC cancer · 2025Article
- Research progress of drug resistance mechanism of temozolomide in the treatment of glioblastoma.Heliyon · 2024Review
- Targeting glioblastoma tumor hyaluronan to enhance therapeutic interventions that regulate metabolic cell properties.Advanced therapeutics · 2024Article
- Synthesis and new DNA targeting activity of 6- and 7-tert-butylfascaplysins.Scientific reports · 2024Article
- Article
- Review
- Article
- G2 checkpoint targeting via Wee1 inhibition radiosensitizes EGFRvIII-positive glioblastoma cells.Radiation oncology (London, England) · 2023Article
- Characteristics of glioblastomas and immune microenvironment in a Chinese family with Lynch syndrome and concurrent porokeratosis.Frontiers in oncology · 2023Article
- Characterization of EGFR-reprogrammable temozolomide-resistant cells in a model of glioblastoma.Cell death discovery · 2022Article
- Phenotypical Flexibility of the EGFRvIII-Positive Glioblastoma Cell Line and the Multidirectional Influence of TGFβ and EGF on These Cells-EGFRvIII Appears as a Weak Oncogene.International journal of molecular sciences · 2022Article
- Cytotoxic N-Methylpretrichodermamide B Reveals Anticancer Activity and Inhibits P-Glycoprotein in Drug-Resistant Prostate Cancer Cells.Marine drugs · 2022Article
- Identification of potential targets of the curcumin analog CCA-1.1 for glioblastoma treatment : integrated computational analysis and in vitro study.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 3 countries.
Funding
Abstract
The oncogene epidermal growth factor receptor variant III (EGFRvIII) is frequently expressed in glioblastomas (GBM) but its impact on therapy response is still under controversial debate. Here we wanted to test if EGFRvIII influences the sensitivity towards the alkylating agent temozolomide (TMZ). Therefore, we retrospectively analyzed the survival of 336 GBM patients, demonstrating that under standard treatment, which includes TMZ, EGFRvIII expression is associated with prolonged survival, but only in patients with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylated tumors. Using isogenic GBM cell lines with endogenous EGFRvIII expression we could demonstrate that EGFRvIII increases TMZ sensitivity and results in enhanced numbers of DNA double-strand breaks and a pronounced S/G2-phase arrest after TMZ treatment. We observed a higher expression of DNA mismatch repair (MMR) proteins in EGFRvIII+ cells and patient tumor samples, which was most pronounced for MSH2 and MSH6. EGFRvIII-specific knockdown reduced MMR protein expression thereby increasing TMZ resistance. Subsequent functional kinome profiling revealed an increased activation of p38- and ERK1/2-dependent signaling in EGFRvIII expressing cells, which regulates MMR protein expression downstream of EGFRvIII. In summary, our results demonstrate that the oncoprotein EGFRvIII sensitizes a fraction of GBM to current standard of care treatment through the upregulation of DNA MMR.
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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 Socratic graph.