ArticleCancer discovery2014
ATM regulates 3-methylpurine-DNA glycosylase and promotes therapeutic resistance to alkylating agents.
Article in Cancer discovery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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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.
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Who cites it
52 citing papers in PubMed, 70 citations in OpenAlex.
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- Decoding and Overcoming Temozolomide Resistance Through CRISPR/Cas Technologies.Molecular diagnosis & therapy · 2026Review
- E3 ligase LMO7 promotes ALKBH2 ubiquitination to sensitize MGMT-deficient glioblastoma to temozolomide.Cell death & disease · 2026Article
- Proinflammatory macrophage secretome enhances temozolomide sensitivity in glioblastoma via pSTAT3-mediated downregulation of DNA repair enzymes.Scientific reports · 2025Article
- Refined DNA repair manipulation enables a universal knock-in strategy in mouse embryos.Nature communications · 2025Article
- DNA polymerase beta expression in head & neck cancer modulates the poly(ADP-ribose)-mediated replication checkpoint.DNA repair · 2025Article
- A novel nuclear RNA HSD52 scaffolding NONO/SFPQ complex modulates DNA damage repair to facilitate temozolomide resistance.Neuro-oncology · 2025Article
- Chloride Intracellular Channel 1 Enhances Glioblastoma Cell Migration and Epithelial-Mesenchymal Transition by Activating the ERK1/2 Signaling Pathway.Current protein & peptide science · 2025Article
- Host RNA NMolecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Article
- Mammalian target of rapamycin inhibition protects glioma cells from temozolomide-induced cell death.Cell death discovery · 2024Article
- Identification of DNA methylation-regulated WEE1 with potential implications in prognosis and immunotherapy for low-grade glioma.Cancer biomarkers : section A of Disease markers · 2024Article
- Lysine-specific histone demethylase 1A (KDM1A/LSD1) inhibition attenuates DNA double-strand break repair and augments the efficacy of temozolomide in glioblastoma.Neuro-oncology · 2023Article
- Experimental study of selective MGMT peptides mimicking TMZ drug resistance in glioma.Biochemistry and biophysics reports · 2022Article
- Review
- Bortezomib abrogates temozolomide-induced autophagic flux through an ATG5 dependent pathway.Frontiers in cell and developmental biology · 2022Article
- Base excision repair accessory factors in senescence avoidance and resistance to treatments.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Prrx1 promotes resistance to temozolomide by upregulating ABCC1 and inducing vasculogenic mimicry in glioma.American journal of cancer research · 2022Article
- Genotoxic therapy and resistance mechanism in gliomas.Pharmacology & therapeutics · 2021Review
- NADNAR cancer · 2021Article
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Authors and funding
21 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledAlkylating agents are a first-line therapy for the treatment of several aggressive cancers, including pediatric glioblastoma, a lethal tumor in children. Unfortunately, many tumors are resistant to this therapy. We sought to identify ways of sensitizing tumor cells to alkylating agents while leaving normal cells unharmed, increasing therapeutic response while minimizing toxicity. Using an siRNA screen targeting over 240 DNA damage response genes, we identified novel sensitizers to alkylating agents. In particular, the base excision repair (BER) pathway, including 3-methylpurine-DNA glycosylase (MPG), as well as ataxia telangiectasia mutated (ATM), were identified in our screen. Interestingly, we identified MPG as a direct novel substrate of ATM. ATM-mediated phosphorylation of MPG was required for enhanced MPG function. Importantly, combined inhibition or loss of MPG and ATM resulted in increased alkylating agent-induced cytotoxicity in vitro and prolonged survival in vivo. The discovery of the ATM-MPG axis will lead to improved treatment of alkylating agent-resistant tumors. SIGNIFICANCE: Inhibition of ATM and MPG-mediated BER cooperate to sensitize tumor cells to alkylating agents, impairing tumor growth in vitro and in vivo with no toxicity to normal cells, providing an ideal therapeutic window.
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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.