ArticleJournal of the National Cancer Institute2021
Pathogenic ATM Mutations in Cancer and a Genetic Basis for Radiotherapeutic Efficacy.
Article in Journal of the National Cancer Institute, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed, 63 citations in OpenAlex.
- Lutetium-177-PSMA-617 or cabazitaxel in metastatic prostate cancer: circulating tumor DNA analysis of the randomized phase 2 TheraP trial.Nature medicine · 2025Trial
- Clinical Impact of Germline Pathogenic Variants in High-risk Prostate Cancer Treated with Radiotherapy.European urology open science · 2026Article
- A ferroptosis-suppressive state drives resistance to bladder-preserving chemoradiotherapy in muscle-invasive bladder cancer.Signal transduction and targeted therapy · 2026Article
- Ataxia telangiectasia mutated (ATM) kinase as a predictive biomarker in clinical oncology: implications for a precision treatment approach.Neoplasia (New York, N.Y.) · 2026Review
- Radiotherapy Response Prediction in Myxofibrosarcomas and Undifferentiated Soft Tissue Sarcomas Using DNA Methylation and Copy Number Profiling.International journal of surgical pathology · 2026Article
- Anti-trapping scaffold protein: significance in cancer cell innate immune signaling and opportunities for immunotherapy.Frontiers in immunology · 2026Review
- Personalizing cancer therapy: the role of pharmacogenetics in overcoming drug resistance and toxicity.Molecular biology reports · 2025Review
- AlphaMissense for Identifying Pathogenic Missense Mutations in DNA Damage Repair Genes in Cancer.JCO precision oncology · 2025Article
- The cold immunological landscape of ATM-deficient cancers.Journal for immunotherapy of cancer · 2025Article
- Long-Term Survival Following Chemoradiation in Locoregional Recurrent GermlineAdvances in radiation oncology · 2025Article
- Selective Modulation of Osteoclast Function byToxins · 2025Article
- A woman with a pleural mesothelioma and an inheritedAnnals of translational medicine · 2025Article
- Tumor sequencing before and after neoadjuvant chemoradiotherapy in locally advanced rectal cancer: Genetic tumor characterization and clinical outcome.Clinical and translational radiation oncology · 2025Article
- Genotype-Directed Synthetic Cytotoxicity of ATR Inhibition with Radiotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Breast cancer and ATM mutations: treatment implications.Hereditary cancer in clinical practice · 2024Review
- Advancements in Early Detection and Screening Strategies for Pancreatic Cancer: From Genetic Susceptibility to Novel Biomarkers.Journal of clinical medicine · 2024Review
- GTP Signaling Links Metabolism, DNA Repair, and Responses to Genotoxic Stress.Cancer discovery · 2024Article
- The art of war: using genetic insights to understand and harness radiation sensitivity in hematologic malignancies.Frontiers in oncology · 2024Review
- Effects of Ataxia-Telangiectasia Mutated Variants on Radionecrosis and Local Control After Stereotactic Radiation Surgery for Non-Small Cell Lung Cancer Brain Metastases.Advances in radiation oncology · 2024Article
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31 authors at 1 institution in 1 country.
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Abstract
backgroundRadiation therapy is one of the most commonly used cancer therapeutics but genetic determinants of clinical benefit are poorly characterized. Pathogenic germline variants in ATM are known to cause ataxia-telangiectasia, a rare hereditary syndrome notable for marked radiosensitivity. In contrast, somatic inactivation of ATM is a common event in a wide variety of cancers, but its clinical actionability remains obscure.
methodsWe analyzed 20 107 consecutively treated advanced cancer patients who underwent targeted genomic sequencing as part of an institutional genomic profiling initiative and identified 1085 harboring a somatic or germline ATM mutation, including 357 who received radiotherapy (RT). Outcomes of irradiated tumors harboring ATM loss-of-function (LoF) mutations were compared with those harboring variants of unknown significance. All statistical tests were 2-sided.
resultsAmong 357 pan-cancer patients who received 727 courses of RT, genetic inactivation of ATM was associated with improved radiotherapeutic efficacy. The 2-year cumulative incidence of irradiated tumor progression was 13.2% vs 27.5% for tumors harboring an ATM LoF vs variant of unknown significance allele, respectively (hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.34 to 0.77, P = .001). The greatest clinical benefit was seen in tumors harboring biallelic ATM inactivation (HR = 0.19, 95% CI = 0.06 to 0.60, P = .005), with statistically significant benefit also observed in tumors with monoallelic ATM inactivation (HR = 0.57, 95% CI = 0.35 to 0.92, P = .02). Notably, ATM LoF was highly predictive of outcome in TP53 wild-type tumors but not among TP53-mutant tumors.
conclusionsWe demonstrate that somatic ATM inactivation is associated with markedly improved tumor control following RT. The identification of a radio-sensitive tumor phenotype across multiple cancer types offers potential clinical opportunities for genomically guided RT.
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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.