Targeting Werner Helicase: A novel combination strategy for MSI colorectal cancer

Colorectal cancer (CRC) is a highly heterogeneous disease characterized by genetic and epigenetic abnormalities. The microsatellite instability (MSI) CRC demonstrates a strong responsiveness to immunotherapy. Despite advancements in immunotherapy have markedly improved the prognosis of MSI CRC patients over the past two decades, resistance to treatment has emerged as a major clinical challenge. Werner syndrome ATP-dependent helicase (WRN), a member of the RecQ helicase family, plays critical roles in telomere maintenance, DNA replication, repair, and other essential cellular processes. Recent research has identified WRN as a synthetic lethal vulnerability in MSI cancers. Targeting WRN represents a promising approach for overcoming immunotherapy resistance in MSI CRC. In this review, we explore the physiological and pathological functions of WRN, and evaluate the potential benefits and limitations of WRN inhibitors as a therapeutic strategy for MSI CRC patients.