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WRN Inhibitor Exploits Synthetic Lethal Weakness in MSI Cancers
Key Takeaways
- A phase 1 trial reported in Nature Medicine tested inhibition of the Werner syndrome helicase (WRN) in cancers with microsatellite instability.
- The approach relies on synthetic lethality: MSI tumors already lack mismatch repair, and blocking WRN removes a second pathway they depend on.
- WRN is a helicase involved in DNA replication, repair, and genome stability, and MSI cells appear more reliant on it than healthy cells.
- Phase 1 studies primarily establish safety, tolerability, dosing and preliminary target engagement rather than proven efficacy.
DE
DT Editorial Team··via nature.com