Article

Functional orthogonality of WRN inhibitor resistance enables alternating therapy and mutation-tolerant inhibitor design in MSI-H cancers

2026-06-12

Abstract excerpt

Werner syndrome helicase (WRN) is a synthetic-lethal vulnerability in microsatellite instability–high (MSI-H)/mismatch repair–deficient (dMMR) cancers 1–5 , and non-covalent and covalent WRN inhibitors are now entering clinical development 6–9 . A central unresolved question is whether resistance to one WRN inhibitor class inevitably compromises the target, or instead creates actionable vulnerabilities to an alt...

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Literature Corpus work: 1dc596c8-efb7-5fff-938e-8f3fea65166c
DOI: 10.64898/2026.06.09.731233

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