ArticleCell reports2016
Cancer-Specific Synthetic Lethality between ATR and CHK1 Kinase Activities.
Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 61 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
61 citing papers in PubMed, 146 citations in OpenAlex.
- Divergent Roles of Canonical and Non-Canonical Mismatch Repair in Regulating Temozolomide Sensitivity in Glioblastoma.International journal of molecular sciences · 2026Review
- Aging and cancer: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Combination of CHK1 and CHK2 inhibitors exerts synergistic antitumor effects against neuroblastoma cells.Pediatric research · 2026Article
- The DNA-PKcs/JNK/p53 pathway underlies changes in cell fate decision toward death during DNA replication catastrophe.Nucleic acids research · 2025Article
- Cancer Vulnerabilities Through Targeting the ATR/Chk1 and ATM/Chk2 Axes in the Context of DNA Damage.Cells · 2025Review
- Comprehensive bioinformatics analysis of omics data to reveal molecular mechanisms and biomarkers in multiple cancers.In silico pharmacology · 2025Article
- Combined MEK1/2 and ATR inhibition promotes myeloma cell death through a STAT3-dependent mechanism in vitro and in vivo.British journal of haematology · 2024Article
- Review
- Clinical translation for targeting DNA damage repair in non-small cell lung cancer: a review.Translational lung cancer research · 2024Review
- APOBEC3A induces DNA gaps through PRIMPOL and confers gap-associated therapeutic vulnerability.Science advances · 2024Article
- Discovery of Ruthenium(II) Metallocompound and Olaparib Synergy for Cancer Combination Therapy.Journal of medicinal chemistry · 2023Article
- NUDT22 promotes cancer growth through pyrimidine salvage.Oncogene · 2023Article
- The Combination of ATM and Chk1 Inhibitors Induces Synthetic Lethality in Colorectal Cancer Cells.Cancers · 2023Article
- Ring finger protein 126 promotes breast cancer metastasis and serves as a potential target to improve the therapeutic sensitivity of ATR inhibitors.Breast cancer research : BCR · 2022Article
- Multiple-low-dose therapy: effective killing of high-grade serous ovarian cancer cells with ATR and CHK1 inhibitors.NAR cancer · 2022Article
- Overexpressed c-Myc Sensitizes Cells to TH1579, a Mitotic Arrest and Oxidative DNA Damage Inducer.Biomolecules · 2022Article
- DNA Damage Response in Cancer Therapy and Resistance: Challenges and Opportunities.International journal of molecular sciences · 2022Review
- Resistance to ATR Inhibitors Is Mediated by Loss of the Nonsense-Mediated Decay Factor UPF2.Cancer research · 2022Article
- SLOAD: a comprehensive database of cancer-specific synthetic lethal interactions for precision cancer therapy via multi-omics analysis.Database : the journal of biological databases and curation · 2022Article
- Novel Therapeutic Approaches with DNA Damage Response Inhibitors for Melanoma Treatment.Cells · 2022Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ATR and CHK1 maintain cancer cell survival under replication stress and inhibitors of both kinases are currently undergoing clinical trials. As ATR activity is increased after CHK1 inhibition, we hypothesized that this may indicate an increased reliance on ATR for survival. Indeed, we observe that replication stress induced by the CHK1 inhibitor AZD7762 results in replication catastrophe and apoptosis, when combined with the ATR inhibitor VE-821 specifically in cancer cells. Combined treatment with ATR and CHK1 inhibitors leads to replication fork arrest, ssDNA accumulation, replication collapse, and synergistic cell death in cancer cells in vitro and in vivo. Inhibition of CDK reversed replication stress and synthetic lethality, demonstrating that regulation of origin firing by ATR and CHK1 explains the synthetic lethality. In conclusion, this study exemplifies cancer-specific synthetic lethality between two proteins in the same pathway and raises the prospect of combining ATR and CHK1 inhibitors as promising cancer therapy.
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.