Article
Microsatellite Instable Cancer Cells Acquire On-target Resistance Mutations to WRN Helicase Inhibitors.
Molecular cancer therapeutics - 4 Aug 2026
Fowler Faith, Gajda Jessica, Mafi Amirhossein, Kelly Aileen, Jeffries Cynthia L, Le Phuong, Shi Lei, George Mariam, Elsen Nathaniel, Korepanova Alla V, Zerbs Sarah M, Pemberton Orville A, Xu Xiangdong, Gesmundo Nathan, Qiu Wei, Han Fei, Tang Henry, Panchal Sanjay C, Dart Michael, Hickson Jonathan, Sun Chaohong, Tong Yunsong, Firestone Ari J
Abstract excerpt
The Werner syndrome helicase (WRN) is a promising target for cancers with microsatellite instability (MSI), leading to the initiation of at least five phase I clinical trials. Acquired resistance is a substantial obstacle to obtaining lasting benefits from targeted therapies in oncology and may be particularly acute in the setting of mismatch repair-deficient (dMMR) tumors, which can sample increased fitness...
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