ArticleJCI insight2024
ATR inhibition radiosensitizes cells through augmented DNA damage and G2 cell cycle arrest abrogation.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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
17 citing papers in PubMed.
- Targeting the DNA Damage Response in Cancer.MedComm · 2026Review
- Safety and efficacy of ceralasertib, an ATR kinase inhibitor, combined with olaparib: dose escalation in advanced solid tumours and dose expansion in advanced breast cancer.British journal of cancer · 2026Article
- DONSON links tumor-cell survival to MIF-associated macrophage remodeling in small cell lung cancer.Apoptosis : an international journal on programmed cell death · 2026Article
- DDX21 Enhances Radiosensitivity in Head and Neck Squamous Cell Carcinoma by Suppressing MK2-Mediated DNA Damage Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Phase 1 study of ceralasertib, an ATR kinase inhibitor, in combination with durvalumab in patients with recurrent or metastatic NSCLC or HNSCC.British journal of cancer · 2026Article
- Berzosertib enhances the sensitivity of pediatric diffuse midline glioma H3K27-altered cells to radiotherapy.Cell death & disease · 2026Article
- Synergistic nanomedicine overcomes hypoxia-driven DNA repair to potentiate radiotherapy for lung adenocarcinoma.Theranostics · 2026Article
- Synthetic lethality in cancer therapy: Mechanisms, models and clinical translation for overcoming therapeutic resistance.Clinical and translational medicine · 2026Review
- Inhibition of ATM, ATR and DNA-PK radiosensitises 3D uveal melanoma models to X-rays and proton beam therapy.Frontiers in oncology · 2026Article
- Glutamine metabolism and its roles in tumor radiotherapy by regulating DNA damage repair.Frontiers in cell and developmental biology · 2026Review
- Article
- Hybrid biomaterials-based radiosensitizers: Preparations and their applications in enhancing tumor radiotherapy.Materials today. Bio · 2025Article
- Understanding and Exacerbating the Biological Response of Uveal Melanoma to Proton Beam Therapy.Cancers · 2025Review
- Genome-wide association study uncovers a novel gene responsible for rice seedling submergence tolerance.Plant biotechnology journal · 2025Article
- Synthetic Lethality-Based Targets and Their Exploration in Tumour Combination Strategies.Journal of cellular and molecular medicine · 2025Review
- ATR Deficiency Impairs DNA Damage Repair and Accelerates Cellular Senescence in Bovine Mammary Epithelial Cells, Leading to Lactation Dysfunction.Animals : an open access journal from MDPI · 2025Article
- Particle Therapy to Overcome Cancer Radiation Resistance: "ARCHADE" Consortium Updates in Radiation Biology.Cancers · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Ataxia telangiectasia and Rad3-related protein (ATR) is a key DNA damage response protein that facilitates DNA damage repair and regulates cell cycle progression. As such, ATR is an important component of the cellular response to radiation, particularly in cancer cells, which show altered DNA damage response and aberrant cell cycle checkpoints. Therefore, ATR's pharmacological inhibition could be an effective radiosensitization strategy to improve radiotherapy. We assessed the ability of an ATR inhibitor, AZD6738, to sensitize cancer cell lines of various histologic types to photon and proton radiotherapy. We found that radiosensitization took place through persistent DNA damage and abrogated G2 cell cycle arrest. We also found that AZD6738 increased the number of micronuclei after exposure to radiotherapy. We found that combining radiation with AZD6738 led to tumor growth delay and prolonged survival relative to radiation alone in a breast cancer model. Combining AZD6738 with photons or protons also led to increased macrophage infiltration at the tumor microenvironment. These results provide a rationale for further investigation of ATR inhibition in combination with radiotherapy and with other agents such as immune checkpoint blockade.
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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.