Research Progress on the Synthetic Lethal New Target WRN in Microsatellite Instability Malignant Tumors

Microsatellite instability(MSI) is a phenomenon in which new microsatellite alleles arise due to impaired or defective DNA mismatch repair in tumor cells. As one of the recognized important oncogenic pathways, MSI can lead to further disorder and mutation of tumor cell genome, thereby promoting the occurrence and development of malignant tumors. Werner syndrome protein (WRN) helicase, belonging to the RecQ family, plays an important role in DNA repair and maintenance of genome stability. Recent studies have discovered that the growth of malignancies with MSI is significantly reliant on WRN helicase, suggesting that targeting WRN could be a promising approach for developing therapies against MSI-associated cancers. Therefore, this review aims to conduct a systematic review of the structure and biological functions of WRN helicase, which is a new target for synthetic lethality. Additionally, latest progress on WRN helicase inhibitors are overviewed with the goal of providing a reference for the treatment of MSI malignant tumors and the development of WRN inhibitors.