ArticleCancer research2014
ATR pathway inhibition is synthetically lethal in cancer cells with ERCC1 deficiency.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
What it found
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Who cites it
86 citing papers in PubMed, 137 citations in OpenAlex.
- Ataxia-Telangiectasia, DNA Repair Deficits, Immune Dysfunction, and Cancer: A Review of Mechanisms, Clinical Presentations, and Emerging Therapies.Clinical reviews in allergy & immunology · 2026Review
- Replication stress in cancer: origins, consequences and therapeutic opportunities.Nature reviews. Cancer · 2026Review
- A Unique Chimeric RNA: ERCC1-iASPP Drives Benzo[a]pyrene-Induced Lung Carcinogenesis via Dual Coding and Non-Coding Mechanisms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Implications of DNA damage response and immunotherapy in tumor therapy.Cell communication and signaling : CCS · 2025Review
- Ubiquitin-specific protease 15 interacts directly with the HSV-1 alkaline nuclease and facilitates viral recombination and replication fork stability.Journal of virology · 2025Article
- Cancer Vulnerabilities Through Targeting the ATR/Chk1 and ATM/Chk2 Axes in the Context of DNA Damage.Cells · 2025Review
- PARP inhibition-associated heterochromatin confers increased DNA replication stress and vulnerability to ATR inhibition in SMARCA4-deficient cells.Cell death discovery · 2025Article
- KLF5 loss sensitizes cells to ATR inhibition and is synthetic lethal with ARID1A deficiency.Nature communications · 2025Article
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- The Novel ATR Inhibitor M1774 Induces Replication Protein Overexpression and Broad Synergy with DNA-targeted Anticancer Drugs.Molecular cancer therapeutics · 2024Article
- Targeting ATR in patients with cancer.Nature reviews. Clinical oncology · 2024Review
- Unveiling Novel ERCC1-XPF Complex Inhibitors: Bridging the Gap from In Silico Exploration to Experimental Design.International journal of molecular sciences · 2024Article
- Durable responses to ATR inhibition with ceralasertib in tumors with genomic defects and high inflammation.The Journal of clinical investigation · 2024Article
- Application and research progress of synthetic lethality in the development of anticancer therapeutic drugs.Frontiers in oncology · 2024Review
- Review
- Dysfunction of ubiquitin protein ligaseNAR cancer · 2023Article
- Novel Cellular Functions of ATR for Therapeutic Targeting: Embryogenesis to Tumorigenesis.International journal of molecular sciences · 2023Review
- Emerging strategies for cancer therapy by ATR inhibitors.Cancer science · 2023Review
- Camonsertib in DNA damage response-deficient advanced solid tumors: phase 1 trial results.Nature medicine · 2023Article
26 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
3 authors at 1 institution in 1 country.
Funding
Abstract
The DNA damage response kinase ATR and its effector kinase CHEK1 are required for cancer cells to survive oncogene-induced replication stress. ATR inhibitors exhibit synthetic lethal interactions, with deficiencies in the DNA damage response enzymes ATM and XRCC1 and with overexpression of the cell cycle kinase cyclin E. Here, we report a systematic screen to identify synthetic lethal interactions with ATR pathway-targeted drugs, rationalized by their predicted therapeutic utility in the oncology clinic. We found that reduced function in the ATR pathway itself provided the strongest synthetic lethal interaction. In addition, we found that loss of the structure-specific endonuclease ERCC1-XPF (ERCC4) is synthetic lethal with ATR pathway inhibitors. ERCC1-deficient cells exhibited elevated levels of DNA damage, which was increased further by ATR inhibition. When treated with ATR or CHEK1 inhibitors, ERCC1-deficient cells were arrested in S-phase and failed to complete cell-cycle transit even after drug removal. Notably, triple-negative breast cancer cells and non-small cell lung cancer cells depleted of ERCC1 exhibited increased sensitivity to ATR pathway-targeted drugs. Overall, we concluded that ATR pathway-targeted drugs may offer particular utility in cancers with reduced ATR pathway function or reduced levels of ERCC4 activity.
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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.