ArticleCell cycle (Georgetown, Tex.)2013
Targeting an Achilles' heel of cancer with a WRN helicase inhibitor.
Article in Cell cycle (Georgetown, Tex.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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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.
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Who cites it
36 citing papers in PubMed, 64 citations in OpenAlex.
- Article
- Novel WRN Helicase Inhibitors Selectively Target Microsatellite-Unstable Cancer Cells.Cancer discovery · 2024Article
- Replication stress as a driver of cellular senescence and aging.Communications biology · 2024Review
- Article
- Review
- WRN rescues replication forks compromised by a BRCA2 deficiency: Predictions for how inhibition of a helicase that suppresses premature aging tilts the balance to fork demise and chromosomal instability in cancer.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Article
- Synthetic Lethal Interactions of RECQ Helicases.Trends in cancer · 2021Review
- Structure of the helicase core of Werner helicase, a key target in microsatellite instability cancers.Life science alliance · 2021Article
- Article
- Inhibition of DNA Repair in Cancer Therapy: Toward a Multi-Target Approach.International journal of molecular sciences · 2020Review
- Article
- Article
- Werner Syndrome Helicase Is Required for the Survival of Cancer Cells with Microsatellite Instability.iScience · 2019Article
- Review
- A high-throughput screen to identify novel small molecule inhibitors of the Werner Syndrome Helicase-Nuclease (WRN).PloS one · 2019Article
- Cellular Assays to Study the Functional Importance of Human DNA Repair Helicases.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Review
- Clinically Applicable Inhibitors Impacting Genome Stability.Molecules (Basel, Switzerland) · 2018Review
- New Insights Into DNA Helicases as Druggable Targets for Cancer Therapy.Frontiers in molecular biosciences · 2018Review
- Article
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 2 countries.
Funding
Abstract
Our recently published work suggests that DNA helicases such as the Werner syndrome helicase (WRN) represent a novel class of proteins to target for anticancer therapy. Specifically, pharmacological inhibition of WRN helicase activity in human cells defective in the Fanconi anemia (FA) pathway of interstrand cross-link (ICL) repair are sensitized to the DNA cross-linking agent and chemotherapy drug mitomycin C (MMC) by the WRN helicase inhibitor NSC 617145. (1) The mechanistic basis for the synergistic interaction between NSC 617145 and MMC is discussed in this paper and extrapolated to potential implications for genetic or chemically induced synthetic lethality provoked by cellular exposure to the WRN helicase inhibitor under the context of relevant DNA repair deficiencies associated with cancers or induced by small-molecule inhibitors. Experimental data are presented showing that small-molecule inhibition of WRN helicase elevates sensitivity to MMC-induced stress in human cells that are deficient in both FANCD2 and DNA protein kinase catalytic subunit (DNA-PKcs). These findings suggest a model in which drug-mediated inhibition of WRN helicase activity exacerbates the deleterious effects of MMC-induced DNA damage when both the FA and NHEJ pathways are defective. We conclude with a perspective for the FA pathway and synthetic lethality and implications for DNA repair helicase inhibitors that can be developed for anticancer strategies.
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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.