ArticleFrontiers in oncology2012
Repair of 3-methyladenine and abasic sites by base excision repair mediates glioblastoma resistance to temozolomide.
Article in Frontiers in oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
29 citing papers in PubMed, 48 citations in OpenAlex.
- Single-nucleotide-resolution genomic maps of O6-methylguanine from the glioblastoma drug temozolomide.Nucleic acids research · 2025Article
- The interplay of mitochondrial dysfunction and altered metabolic pathways in glioblastoma.Contemporary oncology (Poznan, Poland) · 2025Review
- Characterizing inhibitors of human AP endonuclease 1.PloS one · 2023Article
- An overview of glioblastoma multiforme and temozolomide resistance: can LC-MS-based proteomics reveal the fundamental mechanism of temozolomide resistance?Frontiers in oncology · 2023Review
- Advancements, Challenges, and Future Directions in Tackling Glioblastoma Resistance to Small Kinase Inhibitors.Cancers · 2022Review
- siRNA nanoparticle suppresses drug-resistant gene and prolongs survival in an orthotopic glioblastoma xenograft mouse model.Advanced functional materials · 2021Article
- Involvement of N-methylpurine DNA glycosylase in resistance to temozolomide in patient-derived glioma cells.Scientific reports · 2020Article
- Biological Basis for Threshold Responses to Methylating Agents.Chemical research in toxicology · 2020Review
- PARP inhibition suppresses the emergence of temozolomide resistance in a model system.Journal of neuro-oncology · 2020Article
- Inhibitors of DNA Glycosylases as Prospective Drugs.International journal of molecular sciences · 2020Review
- The DNA repair enzyme MUTYH potentiates cytotoxicity of the alkylating agent MNNG by interacting with abasic sites.The Journal of biological chemistry · 2020Article
- Cell Death Triggered by the Autophagy Inhibitory Drug 3-Methyladenine in Growing Conditions Proceeds With DNA Damage.Frontiers in pharmacology · 2020Article
- DNA-Protein Cross-Link Formation in Nucleosome Core Particles Treated with Methyl Methanesulfonate.Chemical research in toxicology · 2019Article
- Reactivity of N3-Methyl-2'-Deoxyadenosine in Nucleosome Core Particles.Chemical research in toxicology · 2019Article
- Configurational and Conformational Equilibria of NChemical research in toxicology · 2018Article
- C1q/TNF-related peptide 8 (CTRP8) promotes temozolomide resistance in human glioblastoma.Molecular oncology · 2018Article
- Article
- Glioblastoma Recurrence Correlates With Increased APE1 and Polarization Toward an Immuno-Suppressive Microenvironment.Frontiers in oncology · 2018Article
- Mechanism of RNA polymerase II stalling by DNA alkylation.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Drugging the Cancers Addicted to DNA Repair.Journal of the National Cancer Institute · 2017Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Alkylating agents have long played a central role in the adjuvant therapy of glioblastoma (GBM). More recently, inclusion of temozolomide (TMZ), an orally administered methylating agent with low systemic toxicity, during and after radiotherapy has markedly improved survival. Extensive in vitro and in vivo evidence has shown that TMZ-induced O(6)-methylguanine (O(6)-meG) mediates GBM cell killing. Moreover, low or absent expression of O(6)-methylguanine-DNA methyltransferase (MGMT), the sole human repair protein that removes O(6)-meG from DNA, is frequently associated with longer survival in GBMs treated with TMZ, promoting interest in developing inhibitors of MGMT to counter resistance. However, the clinical efficacy of TMZ is unlikely to be due solely to O(6)-meG, as the agent produces approximately a dozen additional DNA adducts, including cytotoxic N3-methyladenine (3-meA) and abasic sites. Repair of 3-meA and abasic sites, both of which are produced in greater abundance than O(6)-meG, is mediated by the base excision repair (BER) pathway, and occurs independently of removal of O(6)-meG. These observations indicate that BER activities are also potential targets for strategies to potentiate TMZ cytotoxicity. Here we review the evidence that 3-meA and abasic sites mediate killing of GBM cells. We also present in vitro and in vivo evidence that alkyladenine-DNA glycosylase, the sole repair activity that excises 3-meA from DNA, and Ape1, the major human abasic site endonuclease, mediate TMZ resistance in GBMs and represent potential anti-resistance targets.
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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.