Microsatellite Unstable Colorectal Cancers: Key Gene Mutation for Werner Helicase Inhibitor Resistance Identified

Although one in five colorectal cancers having microsatellite instability and expressing the Werner Helicase (WRN) gene could be treated with drugs that inhibit WRN, the effectiveness of such an approach has been limited by resistance. However, researchers identified the Cys727 mutation as being solely responsible for WRN inhibitor resistance. This potentially opens the door to using WRN inhibitors in the cancer clinic by inactivating this resistance gene.   At the EORTC-NCI-AACR 2024 Molecular Targets and Cancer Therapeutics Symposium Gabriele Picco, PhD, Senior Staff Scientist in the Translational Cancer Genomics Team at the Wellcome Sanger Institute’s Genome Campus, reported findings about WRN resistance mechanisms that may clear the path to introducing WRN inhibitors to the cancer clinic to fight microsatellite unstable cancers.