ArticleeLife2019
Werner syndrome helicase is a selective vulnerability of microsatellite instability-high tumor cells.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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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.
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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
87 citing papers in PubMed, 138 citations in OpenAlex.
- Targeting WRN Helicase in Microsatellite-Instable Colorectal Cancer Induces Antitumor Immunity through Extrachromosomal Circular DNA Release.Cancer research · 2026Article
- Werner helicase inhibitor for advanced microsatellite instability solid tumors: a phase 1 trial.Nature medicine · 2026Article
- Replication stress in cancer: origins, consequences and therapeutic opportunities.Nature reviews. Cancer · 2026Review
- Suppression of transcription-replication conflicts by sequence-coordinated actions of TRDMT1 and MutLα.Nature communications · 2026Article
- Microsatellite Instable Cancer Cells Acquire On-target Resistance Mutations to WRN Helicase Inhibitors.Molecular cancer therapeutics · 2026Article
- Using cancer profiles to identify synthetic lethal therapeutic targets and predictive biomarkers in cancer gene dependency data.Bioinformatics (Oxford, England) · 2026Article
- dMMR killer: A conditional suicide gene that preferentially kills DNA mismatch repair-deficient cells.Molecular therapy. Nucleic acids · 2026Article
- CRISPR screening redefines therapeutic target identification and drug discovery with precision and scalability.Journal of pharmaceutical analysis · 2026Review
- Design and synthesis of 2-amino-4-(trifluoromethyl)pyrimidine derivatives as potential Werner-dependent antiproliferative agents.Molecular diversity · 2026Article
- Structural insights into WRN helicase reveal conformational states and opportunities for MSI-H cancer drug discovery.Communications biology · 2026Article
- WRN structural flexibility showcased through fragment-based lead discovery of inhibitors.Nature communications · 2026Article
- Synthetic lethality in cancer drug discovery: challenges and opportunities.Nature reviews. Drug discovery · 2026Review
- Identification of VVD-214/RO7589831, a Clinical-Stage, Covalent Allosteric Inhibitor of WRN Helicase for the Treatment of MSI-High Cancers.Journal of medicinal chemistry · 2025Article
- Review
- Loss of UXS1 Selectively Depletes Pyrimidines and Induces Replication Stress in KEAP1-Mutant Lung Cancer.Cancer research · 2025Article
- Targeting DNA Damage Repair Pathways Beyond PARP Inhibition.Targeted oncology · 2025Review
- Therapeutic targeting of mismatch repair-deficient cancers.Nature reviews. Clinical oncology · 2025Review
- Targeting the Werner syndrome protein in microsatellite instability cancers: mechanisms and therapeutic potential.Clinical and experimental medicine · 2025Review
- Exploring the Potential of Homologous Recombination Protein PALB2 in Synthetic Lethal Combinations.ACS chemical biology · 2025Article
- Werner helicase as a therapeutic target in mismatch repair deficient colorectal cancer.DNA repair · 2025Review
27 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
Abstract
Targeted cancer therapy is based on exploiting selective dependencies of tumor cells. By leveraging recent functional screening data of cancer cell lines we identify Werner syndrome helicase (WRN) as a novel specific vulnerability of microsatellite instability-high (MSI-H) cancer cells. MSI, caused by defective mismatch repair (MMR), occurs frequently in colorectal, endometrial and gastric cancers. We demonstrate that WRN inactivation selectively impairs the viability of MSI-H but not microsatellite stable (MSS) colorectal and endometrial cancer cell lines. In MSI-H cells, WRN loss results in severe genome integrity defects. ATP-binding deficient variants of WRN fail to rescue the viability phenotype of WRN-depleted MSI-H cancer cells. Reconstitution and depletion studies indicate that WRN dependence is not attributable to acute loss of MMR gene function but might arise during sustained MMR-deficiency. Our study suggests that pharmacological inhibition of WRN helicase function represents an opportunity to develop a novel targeted therapy for MSI-H cancers.
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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.