Article

On-target mutations confer resistance to WRN helicase inhibitors in Microsatellite Unstable Cancer Cells

2025-12-27

Abstract excerpt

Werner helicase inhibitors (WRNi) are in clinical development for microsatellite-unstable (MSI) tumors with defective DNA mismatch repair. Here, we investigate how cancer cell evolution shapes response to WRN inhibition and informs potential resistance mechanisms. Genome-wide CRISPR screens combined with WRN knockout did not identify bypass mechanisms, underscoring WRN’s essential, non-redundant function in MSI ce...

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Literature Corpus work: fc74df24-25bf-57a6-9d95-2865f45a5757
DOI: 10.64898/2025.12.23.695783

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