ArticleClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2018
Acquired temozolomide resistance in human glioblastoma cell line U251 is caused by mismatch repair deficiency and can be overcome by lomustine.
Article in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Glioblastoma multiforme (GBM): An overview of current therapies and mechanisms of resistance.Pharmacological research · 2021Pooled it
- Convergent adaptive architectures linking chemoresistance and radioresistance in chemoradiotherapy: a systems-level perspective.Frontiers in oncology · 2026Review
- Review
- Revisiting an old therapy for new, promising combinations: Biology and perspectives of lomustine in glioma treatment.Neuro-oncology · 2025Review
- Quercetin Increases Expression of Membrane-TRAIL in Glioblastoma Cells Resulting in Apoptosis.Cancers · 2025Article
- RNA/DNA-binding protein TDP43 regulates DNA mismatch repair genes with implications for genome stability.Nucleic acids research · 2025Article
- RNA/DNA Binding Protein TDP43 Regulates DNA Mismatch Repair Genes with Implications for Genome Stability.bioRxiv : the preprint server for biology · 2025Article
- Acquired resistance to molecularly targeted therapies for cancer.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Temozolomide based treatment in glioblastoma: 6 vs. 12 months.Oncology letters · 2024Article
- Vacuolar Proton-Translocating ATPase May Take Part in the Drug Resistance Phenotype of Glioma Stem Cells.International journal of molecular sciences · 2024Article
- Review
- Ex Vivo Chromosomal Radiosensitivity Testing in Patients with Pathological Germline Variants in Breast Cancer High-Susceptibility GenesCurrent issues in molecular biology · 2023Article
- Triple combination of lomustine, temozolomide and irradiation reduces canine glioma cell survival in vitro.Veterinary medicine and science · 2023Article
- P2X7 receptor antagonism by AZ10606120 significantly reduced in vitro tumour growth in human glioblastoma.Scientific reports · 2023Article
- Temozolomide and Lomustine Induce Tissue Factor Expression and Procoagulant Activity in Glioblastoma Cells In Vitro.Cancers · 2023Article
- Mechanisms of Resistance and Current Treatment Options for Glioblastoma Multiforme (GBM).Cancers · 2023Review
- An overview of glioblastoma multiforme and temozolomide resistance: can LC-MS-based proteomics reveal the fundamental mechanism of temozolomide resistance?Frontiers in oncology · 2023Review
- Characterization of Temozolomide Resistance Using a Novel Acquired Resistance Model in Glioblastoma Cell Lines.Cancers · 2022Article
- Therapeutic Opportunities of Disrupting Genome Integrity in Adult Diffuse Glioma.Biomedicines · 2022Review
- Lomustine and nimustine exert efficient antitumor effects against glioblastoma models with acquired temozolomide resistance.Cancer science · 2021Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeGlioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. While the alkylating agent temozolomide (TMZ) has prolonged overall survival, resistance evolution represents an important clinical problem. Therefore, we studied the effectiveness of radiotherapy and CCNU in an in vitro model of acquired TMZ resistance.
methodsWe studied the MGMT-methylated GBM cell line U251 and its in vitro derived TMZ-resistant subline, U251/TMZ-R. Cytotoxicity of TMZ, CCNU, and radiation was tested. Both cell lines were analyzed for MGMT promotor status and expression of mismatch repair genes (MMR). The influence of MMR inhibition by cadmium chloride (CdCl
resultsDuring the resistance evolution process in vitro, U251/TMZ-R developed MMR deficiency, but MGMT status did not change. U251/TMZ-R cells were more resistant to TMZ than parental U251 cells (cell viability: 92.0% in U251/TMZ-R/69.2% in U251; p = 0.032) yet more sensitive to CCNU (56.4%/80.8%; p = 0.023). The effectiveness of radiotherapy was not reduced in the TMZ-resistant cell line. Combination of CCNU and TMZ showed promising results for both cell lines and overcame resistance. CdCl
conclusionOur results confirm MMR deficiency as a crucial process for resistance evolution to TMZ. MMR-deficient TMZ-resistant GBM cells were particularly sensitive to CCNU and to combined CCNU/TMZ. Effectiveness of radiotherapy was preserved in TMZ-resistant cells. Consequently, CCNU might be preferentially considered as a treatment option for recurrent MGMT-methylated GBM and may even be suitable for prevention of resistance evolution in primary treatment.
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