ArticleTherapeutic advances in medical oncology2020
XRCC1 deficient triple negative breast cancers are sensitive to ATR, ATM and Wee1 inhibitor either alone or in combination with olaparib.
Article in Therapeutic advances in medical oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Targeting ATR offers multifaceted treatment strategies involving RAD51-mediated compensatory DNA repair in bladder cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Medicinal chemistry breakthroughs on ATM, ATR, and DNA-PK inhibitors as prospective cancer therapeutics.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- PARP inhibitor response is enhanced in prostate cancer when XRCC1 expression is reduced.NAR cancer · 2025Article
- Positioning loss of PARP1 activity as the central toxic event in BRCA-deficient cancer.DNA repair · 2024Review
- Small molecule agents for triple negative breast cancer: Current status and future prospects.Translational oncology · 2024Review
- Overexpression of XRCC1 is Associated with Poor Survival in Patients with Head and Neck Squamous Carcinoma and Has Potential to Be Used as Targeted Therapy by Synthetic Lethality.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- Evolving DNA repair synthetic lethality targets in cancer.Bioscience reports · 2022Article
- ATR Inhibitors in Platinum-Resistant Ovarian Cancer.Cancers · 2022Review
- Article
- Association between Olaparib Exposure and Early Toxicity in BRCA-Mutated Ovarian Cancer Patients: Results from a Retrospective Multicenter Study.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Activated STAT3 Is a Novel Regulator of theInternational journal of molecular sciences · 2021Article
- Targeting WEE1 Inhibits Growth of Breast Cancer Cells That Are Resistant to Endocrine Therapy and CDK4/6 Inhibitors.Frontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPARP inhibitor (PARPi) monotherapy is a new strategy in
methodsHighly selective inhibitors of ATR (AZD6738), ATM (AZ31) and Wee1 (AZD1775) either alone or in combination with olaparib were tested for synthetic lethality in XRCC1 deficient TNBC or HeLa cells. Clinicopathological significance of ATR, ATM or Wee1 co-expression in XRCC1 proficient or deficient tumours was evaluated in a large cohort of 1650 human breast cancers.
resultsATR (AZD6738), ATM (AZ31) or Wee1 (AZD1775) monotherapy was selectively toxic in XRCC1 deficient cells. Selective synergistic toxicity was evident when olaparib was combined with AZD6738, AZ31 or AZD1775. The most potent synergistic interaction was evident with the AZD6738 and olaparib combination therapy. In clinical cohorts, ATR, ATM or Wee1 overexpression in XRCC1 deficient breast cancer was associated with poor outcomes.
conclusionXRCC1 stratified DNA repair targeted combinatorial approach is feasible and warrants further clinical evaluation in breast cancer.
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