ArticleNature communications2024
ATM inhibition exploits checkpoint defects and ATM-dependent double strand break repair in TP53-mutant glioblastoma.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed.
- Fluorescent reporter assay reveals ribonucleotides promote mismatch correction in vivo.Nucleic acids research · 2026Article
- Mechanisms, Microenvironments, and Models: Understanding Therapeutic Resistance in Glioblastoma.International journal of radiation oncology, biology, physics · 2026Review
- Divergent Roles of Canonical and Non-Canonical Mismatch Repair in Regulating Temozolomide Sensitivity in Glioblastoma.International journal of molecular sciences · 2026Review
- MET-mediated phosphorylation of YANK2 at Y282 inhibits NEDD4L-dependent SUMOylation and degradation, promoting chemoresistance in glioblastoma.Molecular biomedicine · 2026Article
- Modeling blood-brain barrier-glioblastoma interactions: implications for chemoresistance and therapeutic targeting.Fluids and barriers of the CNS · 2026Review
- Loss of IGF-1R impairs DNA-PKcs recruitment to chromatin leading to defective end-joining.Molecular oncology · 2026Article
- Double strand breaks drive toxicity in a Huntington's disease mouse model with or without somatic expansion.Nature communications · 2026Article
- Loss of JAK1 Function Causes G2-M Cell-Cycle Defects Vulnerable to KIF18A Inhibition.Cancer research · 2026Article
- Low YTHDC1 Expression Upregulates FSCN1 to Promote Nuclear F-Actin Formation and Facilitate Double-strand DNA Breaks Repair in TMZ-Resistant Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting mesenchymal monocyte-derived macrophages to enhance the sensitivity of glioblastoma to temozolomide by inhibiting TNF/CELSR2/p65/Kla-HDAC1/EPAS1 axis.Journal of advanced research · 2026Article
- Impeding the NHEJ Pathway for Overcoming Radioresistance in the Context of Precision Radiotherapy of Cancer.Pharmaceutics · 2026Review
- Next Generation DNA Damage Response Inhibitors: Harnessing Nanocarriers and Tumor Microenvironment for Precision Cancer Therapy.Oncology research · 2026Review
- Article
- PIBF1 (p.R405Q) germline variant identified in cancer susceptibility family impairs protein stability and function.Cancer cell international · 2025Article
- Research progress of DNA damage repair (DDR) and DDR inhibitors in tumor immunotherapy.World journal of surgical oncology · 2025Review
- Comprehensive Measurement of Inter-Individual Variation in DNA Repair Capacity in Healthy Individuals.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Medicinal chemistry breakthroughs on ATM, ATR, and DNA-PK inhibitors as prospective cancer therapeutics.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- CRISPR/Cas9 generated DSB clusters mimic complex lesions induced by high-LET radiation and shift repair from c-NHEJ to mutagenic repair pathways.Scientific reports · 2025Article
- Neurodegeneration rewires the tumor microenvironment via the neuro-immune-cancer axis.iScience · 2025Review
- Differential Clearance of [medRxiv : the preprint server for health sciences · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Determining the balance between DNA double strand break repair (DSBR) pathways is essential for understanding treatment response in cancer. We report a method for simultaneously measuring non-homologous end joining (NHEJ), homologous recombination (HR), and microhomology-mediated end joining (MMEJ). Using this method, we show that patient-derived glioblastoma (GBM) samples with acquired temozolomide (TMZ) resistance display elevated HR and MMEJ activity, suggesting that these pathways contribute to treatment resistance. We screen clinically relevant small molecules for DSBR inhibition with the aim of identifying improved GBM combination therapy regimens. We identify the ATM kinase inhibitor, AZD1390, as a potent dual HR/MMEJ inhibitor that suppresses radiation-induced phosphorylation of DSBR proteins, blocks DSB end resection, and enhances the cytotoxic effects of TMZ in treatment-naïve and treatment-resistant GBMs with TP53 mutation. We further show that a combination of G2/M checkpoint deficiency and reliance upon ATM-dependent DSBR renders TP53 mutant GBMs hypersensitive to TMZ/AZD1390 and radiation/AZD1390 combinations. This report identifies ATM-dependent HR and MMEJ as targetable resistance mechanisms in TP53-mutant GBM and establishes an approach for simultaneously measuring multiple DSBR pathways in treatment selection and oncology research.
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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.