ArticleOpen biology2019
A consensus set of genetic vulnerabilities to ATR inhibition.
Article in Open biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
83 citing papers in PubMed, 112 citations in OpenAlex.
- Ceralasertib Monotherapy in Patients with ATM-Altered Advanced Solid Tumors or Metastatic Castration-Resistant Prostate Cancer: Data from the Phase IIa PLANETTE Study.Cancer research communications · 2026Trial
- Chemogenomic maps reveal a PRDX1-dependent iron-damage axis in the DNA damage response.Nature chemical biology · 2026Article
- G-quadruplex homeostasis is a determinant of PARP inhibitor toxicity in BRCA2-deficient cells.Nature communications · 2026Article
- CIP2A recruits SLX4-MUS81-XPF in mitosis and protects against replication stress.EMBO reports · 2026Article
- Common DNA Damage Response Factors Required for Cellular Resistance to Inhibitors for the Ataxia Telangiectasia and Rad3-Related Checkpoint Kinase in Hematopoietic Cells.Biomolecules · 2026Article
- FET Fusion Oncoproteins Disrupt Physiologic DNA Repair and Create a Targetable Opportunity for ATR Inhibitor Therapy.Cancer research · 2026Article
- Targeting RNase H2: A dual-mechanism strategy to elevate replication stress, DNA damage, and antitumor immunity in TNBC.Cell reports. Medicine · 2026Article
- ATR and PKMYT1 Inhibition Resensitizes a Subset of TNBC Patient-Derived Models to Carboplatin, Inducing Mitotic Catastrophe.Cancer research communications · 2026Article
- ERCC6L2 ensures repair fidelity for staggered-end DNA double-strand breaks.Nature communications · 2026Article
- Pervasive phenotypic effects of FBXO42 are promoted by regulation of PP4 phosphatase.The EMBO journal · 2026Article
- Novel therapeutic potential of the PARP inhibitor talazoparib in synovial sarcoma and its combined effect with ATR inhibitor.Discover oncology · 2026Article
- Pathway for the Development of ATR Inhibitors in Pediatric Malignancies: An ACCELERATE Multistakeholder Analysis.JCO precision oncology · 2026Review
- Accurate prediction of candidate lncRNAs associated with DNA damage response based on gene expression patterns from graph neural networks.Bioinformatics advances · 2026Article
- Targeting ATR offers multifaceted treatment strategies involving RAD51-mediated compensatory DNA repair in bladder cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- The CIP2A-TOPBP1 axis facilitates mitotic DNA repair via MiDAS and MMEJ.Nature communications · 2025Article
- Genetic evidence for PARP1 trapping as a driver of PARP inhibitor efficacy in BRCA mutant cancer cells.Nucleic acids research · 2025Article
- WEE1 inhibitors trigger GCN2-mediated activation of the integrated stress response.Nature communications · 2025Article
- Acquired resistance in cancer: towards targeted therapeutic strategies.Nature reviews. Cancer · 2025Review
- Article
- Phase I trial of ATR inhibitor elimusertib with FOLFIRI in advanced or metastatic gastrointestinal malignancies (ETCTN 10406).Cancer chemotherapy and pharmacology · 2025Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The response to DNA replication stress in eukaryotes is under the control of the ataxia-telangiectasia and Rad3-related (ATR) kinase. ATR responds to single-stranded (ss) DNA to stabilize distressed DNA replication forks, modulate DNA replication firing and prevent cells with damaged DNA or incomplete DNA replication from entering into mitosis. Furthermore, inhibitors of ATR are currently in clinical development either as monotherapies or in combination with agents that perturb DNA replication. To gain a genetic view of the cellular pathways requiring ATR kinase function, we mapped genes whose mutation causes hypersensitivity to ATR inhibitors with genome-scale CRISPR/Cas9 screens. We delineate a consensus set of 117 genes enriched in DNA replication, DNA repair and cell cycle regulators that promote survival when ATR kinase activity is suppressed. We validate 14 genes from this set and report genes not previously described to modulate response to ATR inhibitors. In particular we found that the loss of the POLE3/POLE4 proteins, which are DNA polymerase ε accessory subunits, results in marked hypersensitivity to ATR inhibition. We anticipate that this 117-gene set will be useful for the identification of genes involved in the regulation of genome integrity and the characterization of new biological processes involving ATR, and may reveal biomarkers of ATR inhibitor response in the clinic.
Indexed as
Identifiers
What OpenQuestion holds
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.