ArticleBritish journal of cancer2012
Targeting radiation-resistant hypoxic tumour cells through ATR inhibition.
Article in British journal of cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 164 citations in OpenAlex.
- From bench to bedside: advancing our understanding of radioresistance in rectal cancer.Cancer metastasis reviews · 2026Review
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- HIF-1-regulated TPM3 links hypoxia to motility and invasion beyond the hypoxic fraction in triple-negative breast cancer.NPJ breast cancer · 2026Article
- Generation of Human Haematopoietic Model Cell Lines Revealed Distinct Replication Stress Tolerance Between Two OncogenicBiomolecules · 2026Article
- O-GlcNAcylation of NONO mediates alternative splicing of SETMAR and facilitates NHEJ repair.Genome biology · 2026Article
- Replication Stress in Cancer: Mechanistic Insights and Therapeutic Opportunities for Radiosensitization.Current issues in molecular biology · 2026Review
- Luteolin Enhances Anticancer Effects of PX-478 during Hypoxic Response in Metastatic Breast Cancer Cells.Anti-cancer agents in medicinal chemistry · 2026Article
- 7α-acetoxy-6β-hydroxyroyleanone (Roy) modulates IL-6/STAT3/JAK2 mRNA expression and suppresses tumor growth in glioblastoma cell models.Frontiers in pharmacology · 2026Article
- Auranofin attenuates TOPBP1-mediated ATR replication stress response and improves chemotherapeutic response in breast tumor models.The Journal of clinical investigation · 2025Article
- Medicinal chemistry breakthroughs on ATM, ATR, and DNA-PK inhibitors as prospective cancer therapeutics.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Tumour hypoxia in driving genomic instability and tumour evolution.Nature reviews. Cancer · 2025Review
- Strategies to Overcome Intrinsic and Acquired Resistance to Chemoradiotherapy in Head and Neck Cancer.Cells · 2024Review
- ATR inhibition radiosensitizes cells through augmented DNA damage and G2 cell cycle arrest abrogation.JCI insight · 2024Article
- Hypoxia-Responsive Prodrug of ATR Inhibitor, AZD6738, Selectively Eradicates Treatment-Resistant Cancer Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Inhibition of key DNA double strand break repair protein kinases enhances radiosensitivity of head and neck cancer cells to X-ray and proton irradiation.Cell death discovery · 2024Article
- CHARIOT: a phase I study of berzosertib with chemoradiotherapy in oesophageal and other solid cancers using time to event continual reassessment method.British journal of cancer · 2024Article
- Novel Cellular Functions of ATR for Therapeutic Targeting: Embryogenesis to Tumorigenesis.International journal of molecular sciences · 2023Review
- Invalidity of, and alternative to, the linear quadratic model as a predictive model for postirradiation cell survival.Cancer science · 2023Article
- Targeting the DNA Damage Response and DNA Repair Pathways to Enhance Radiosensitivity in Colorectal Cancer.Cancers · 2022Review
- Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundMost solid tumours contain regions of sub-optimal oxygen concentration (hypoxia). Hypoxic cancer cells are more resistant to radiotherapy and represent the most aggressive fraction of a tumour. It is therefore essential that strategies continue to be developed to target hypoxic cancer cells. Inhibition of the DNA damage response (DDR) might be an effective way of sensitising hypoxic tumour cells to radiotherapy.
methodsHere, we describe the cellular effects of pharmacological inhibition of the apical DDR kinase ATR (Ataxia Telangiectasia and Rad 3 related) with a highly selective inhibitor, VE-821, in hypoxic conditions and its potential as a radiosensitiser.
resultsVE-821 was shown to inhibit ATR-mediated signalling in response to replication arrest induced by severe hypoxia. In these same conditions, VE-821 induced DNA damage and consequently increased Ataxia Telangiectasia Mutated-mediated phosphorylation of H2AX and KAP1. Consistently, ATR inhibition sensitised tumour cell lines to a range of oxygen tensions. Most importantly, VE-821 increased radiation-induced loss of viability in hypoxic conditions. Using this inhibitor we have also demonstrated for the first time a link between ATR and the key regulator of the hypoxic response, HIF-1. HIF-1 stabilisation and transcriptional activity were both decreased in response to ATR inhibition.
conclusionThese findings suggest that ATR inhibition represents a novel strategy to target tumour cells in conditions relevant to pathophysiology and enhance the efficacy of radiotherapy.
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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.