ArticleClinical cancer research : an official journal of the American Association for Cancer Research2008
Mismatch repair deficiency does not mediate clinical resistance to temozolomide in malignant glioma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 82 citations in OpenAlex.
- "One week on-one week off": efficacy and side effects of dose-intensified temozolomide chemotherapy: experiences of a single center.Journal of neuro-oncology · 2013Trial
- Divergent Roles of Canonical and Non-Canonical Mismatch Repair in Regulating Temozolomide Sensitivity in Glioblastoma.International journal of molecular sciences · 2026Review
- Molecular and clinical characteristics of glioma patients with germline pathogenic mutations of Lynch syndrome genes: a large-scale multicenter study.Journal of translational medicine · 2026Article
- Clinicopathologic, molecular and tumor immune microenvironment features of mismatch repair-deficient glioblastomas in Lynch syndrome: a multicenter study of 29 cases with therapeutic implications.Acta neuropathologica communications · 2026Article
- Glioblastoma multiforme: an updated overview of temozolomide resistance mechanisms and strategies to overcome resistance.Discover oncology · 2025Review
- Temozolomide, Procarbazine and Nitrosoureas in the Therapy of Malignant Gliomas: Update of Mechanisms, Drug Resistance and Therapeutic Implications.Journal of clinical medicine · 2023Review
- Influence of MMR, MGMT Promotor Methylation and Protein Expression on Overall and Progression-Free Survival in Primary Glioblastoma Patients Treated with Temozolomide.International journal of molecular sciences · 2023Article
- Sporadic and Lynch syndrome-associated mismatch repair-deficient brain tumors.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Advances in immunotherapy for glioblastoma multiforme.Frontiers in immunology · 2022Review
- Incidence, clinicopathologic, and genetic characteristics of mismatch repair gene-mutated glioblastomas.Journal of neuro-oncology · 2021Article
- Short tandem repeat profiling for the authentication of cancer stem-like cells.International journal of cancer · 2021Article
- Dissecting the mechanism of temozolomide resistance and its association with the regulatory roles of intracellular reactive oxygen species in glioblastoma.Journal of biomedical science · 2021Review
- Temozolomide: An Updated Overview of Resistance Mechanisms, Nanotechnology Advances and Clinical Applications.Current neuropharmacology · 2021Review
- PARP inhibition suppresses the emergence of temozolomide resistance in a model system.Journal of neuro-oncology · 2020Article
- Restoration of Temozolomide Sensitivity by PARP Inhibitors in Mismatch Repair Deficient Glioblastoma is Independent of Base Excision Repair.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Glioblastoma Immune Landscape and the Potential of New Immunotherapies.Frontiers in immunology · 2020Review
- DNA repair genes in astrocytoma tumorigenesis, progression and therapy resistance.Genetics and molecular biology · 2019Article
- Current state of immunotherapy for glioblastoma.Nature reviews. Clinical oncology · 2018Review
- MSH6 haploinsufficiency at relapse contributes to the development of thiopurine resistance in pediatric B-lymphoblastic leukemia.Haematologica · 2018Article
- Immune checkpoint inhibition and its relationship with hypermutation phenoytype as a potential treatment for Glioblastoma.Journal of neuro-oncology · 2017Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
purposeA major mechanism of resistance to methylating agents, including temozolomide, is the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT). Preclinical data indicates that defective DNA mismatch repair (MMR) results in tolerance to temozolomide regardless of AGT activity. The purpose of this study was to determine the role of MMR deficiency in mediating resistance in samples from patients with both newly diagnosed malignant gliomas and those who have failed temozolomide therapy. EXPERIMENTAL
designThe roles of AGT and MMR deficiency in mediating resistance in glioblastoma multiforme were assessed by immunohistochemistry and microsatellite instability (MSI), respectively. The mutation status of the MSH6 gene, a proposed correlate of temozolomide resistance, was determined by direct sequencing and compared with data from immunofluorescent detection of MSH6 protein and reverse transcription-PCR amplification of MSH6 RNA.
resultsSeventy percent of newly diagnosed and 78% of failed-therapy glioblastoma multiforme samples expressed nuclear AGT protein in > or = 20% of cells analyzed, suggesting alternate means of resistance in 20% to 30% of cases. Single loci MSI was observed in 3% of patient samples; no sample showed the presence of high MSI. MSI was not shown to correlate with MSH6 mutation or loss of MSH6 protein expression.
conclusionsAlthough high AGT levels may mediate resistance in a portion of these samples, MMR deficiency does not seem to be responsible for mediating temozolomide resistance in adult malignant glioma. Accordingly, the presence of a fraction of samples exhibiting both low AGT expression and MMR proficiency suggests that additional mechanisms of temozolomide resistance are operational in the clinic.
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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.