ArticleiScience2019
Werner Syndrome Helicase Is Required for the Survival of Cancer Cells with Microsatellite Instability.
Article in iScience, 2019. 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, 134 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
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
- 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
- Prognostic Significance of DNA Repair Gene mRNA Expression in Early-Stage Breast Cancer: Insights into Clinical Relevance.Oncology research · 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
- CRISPR Technology: Transforming the Future of Medicine and Diagnostics.Biochemistry · 2025Review
- Loss of UXS1 Selectively Depletes Pyrimidines and Induces Replication Stress in KEAP1-Mutant Lung Cancer.Cancer research · 2025Article
- Review
- Targeting DNA Damage Repair Pathways Beyond PARP Inhibition.Targeted oncology · 2025Review
- Therapeutic targeting of mismatch repair-deficient cancers.Nature reviews. Clinical oncology · 2025Review
- Ginsenoside Rh2 in combination with IFNγ potentiated the anti-cancer effect by enhancing interferon signaling response in colorectal cancer cells.Acta pharmacologica Sinica · 2025Article
- DNA double-strand break end resection factors and WRN facilitate mitotic DNA synthesis in human cells.Nature communications · 2025Article
- Synthetic Lethality-Based Targets and Their Exploration in Tumour Combination Strategies.Journal of cellular and molecular medicine · 2025Review
- Joint inference of mutational signatures from indels and single-nucleotide substitutions reveals prognostic impact of DNA repair deficiencies.Genome medicine · 2025Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Werner syndrome protein (WRN) is a RecQ enzyme involved in the maintenance of genome integrity. Germline loss-of-function mutations in WRN led to premature aging and predisposition to cancer. We evaluated synthetic lethal (SL) interactions between WRN and another human RecQ helicase, BLM, with DNA damage response genes in cancer cell lines. We found that WRN was SL with a DNA mismatch repair protein MutL homolog 1, loss of which is associated with high microsatellite instability (MSI-H). MSI-H cells exhibited increased double-stranded DNA breaks, altered cell cycles, and decreased viability in response to WRN knockdown, in contrast to microsatellite stable (MSS) lines, which tolerated depletion of WRN. Although WRN is the only human RecQ enzyme with a distinct exonuclease domain, only loss of helicase activity drives the MSI SL interaction. This SL interaction in MSI cancer cells positions WRN as a relevant therapeutic target in patients with MSI-H tumors.
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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.