ArticleCancer research2015
Minor Changes in Expression of the Mismatch Repair Protein MSH2 Exert a Major Impact on Glioblastoma Response to Temozolomide.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.
- Glioblastoma multiforme (GBM): An overview of current therapies and mechanisms of resistance.Pharmacological research · 2021Pooled it
- A phase II randomized, multicenter, open-label trial of continuing adjuvant temozolomide beyond 6 cycles in patients with glioblastoma (GEINO 14-01).Neuro-oncology · 2020Trial
- Trial
- Fluorescent reporter assay reveals ribonucleotides promote mismatch correction in vivo.Nucleic acids research · 2026Article
- Divergent Roles of Canonical and Non-Canonical Mismatch Repair in Regulating Temozolomide Sensitivity in Glioblastoma.International journal of molecular sciences · 2026Review
- Distinct mutational signature and clonal evolution in constitutional mismatch repair deficiency-associated high-grade gliomas.iScience · 2026Article
- Mismatch repair deficiency drives malignant progression and alters the tumor immune microenvironment in glioblastoma models.The Journal of clinical investigation · 2026Article
- Overcoming Chemoresistance in Glioblastoma: Mechanisms, Therapeutic Strategies, and Functional Precision Medicine.International journal of molecular sciences · 2026Review
- Role of matrix metalloproteinases in the invasion of glioblastoma and drug interventions (Review).International journal of molecular medicine · 2026Review
- Selinexor enhances temozolomide efficacy in glioblastoma through modulation of multiple resistance-associated mechanisms.Frontiers in oncology · 2026Article
- Expression of DNA-damage response genes after exposure to high LET particles used in BNCT in glioblastoma cells with altered radiosensitivity.Scientific reports · 2025Article
- Senotherapeutics in Malignant Brain Cancer Therapy.Current oncology reports · 2025Review
- Integrating proteomics and bioinformatics for the identification of breast cancer biomarkers interacting with telomeric G-quadruplex.Cancer cell international · 2025Article
- Post-translational modifications in DNA damage repair: mechanisms underlying temozolomide resistance in glioblastoma.Oncogene · 2025Review
- Purine metabolism rewiring improves glioblastoma susceptibility to temozolomide treatment.Cell death & disease · 2025Article
- Nonrepair functions of DNA mismatch repair proteins: new avenues for precision oncology.Trends in cancer · 2025Review
- Research progress of drug resistance mechanism of temozolomide in the treatment of glioblastoma.Heliyon · 2024Review
- ARF4-mediated retrograde trafficking as a driver of chemoresistance in glioblastoma.Neuro-oncology · 2024Article
- ATM inhibition exploits checkpoint defects and ATM-dependent double strand break repair in TP53-mutant glioblastoma.Nature communications · 2024Article
- CDK-independent role of D-type cyclins in regulating DNA mismatch repair.Molecular cell · 2024Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Glioblastoma (GBM) is often treated with the cytotoxic drug temozolomide, but the disease inevitably recurs in a drug-resistant form after initial treatment. Here, we report that in GBM cells, even a modest decrease in the mismatch repair (MMR) components MSH2 and MSH6 have profound effects on temozolomide sensitivity. RNAi-mediated attenuation of MSH2 and MSH6 showed that such modest decreases provided an unexpectedly strong mechanism of temozolomide resistance. In a mouse xenograft model of human GBM, small changes in MSH2 were sufficient to suppress temozolomide-induced tumor regression. Using The Cancer Genome Atlas to analyze mRNA expression patterns in tumors from temozolomide-treated GBM patients, we found that MSH2 transcripts in primary GBM could predict patient responses to initial temozolomide therapy. In recurrent disease, the absence of microsatellite instability (the standard marker for MMR deficiency) suggests a lack of involvement of MMR in the resistant phenotype of recurrent disease. However, more recent studies reveal that decreased MMR protein levels occur often in recurrent GBM. In accordance with our findings, these reported decreases may constitute a mechanism by which GBM evades temozolomide sensitivity while maintaining microsatellite stability. Overall, our results highlight the powerful effects of MSH2 attenuation as a potent mediator of temozolomide resistance and argue that MMR activity offers a predictive marker for initial therapeutic response to temozolomide treatment.
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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.