Abstract B029: Enhanced anticancer effects through synergistic targeting of DDX5 and DNA damage-related factors

Abstract

Abstract Dead-box RNA helicase 5 (DDX5) is a member of the DDX RNA helicase family, commonly overexpressed in most carcinomas and plays an important role in tumor development and malignant progression. While DDX5 functions as a helicase in cells, it also plays various other roles in DNA damage repair, and resistance to radiotherapy or anticancer drugs. However, due to the diverse functions of DDX5, the anticancer effects solely from inhibiting helicase function of DDX5 are limited. Here, we inhibited DDX5 along with other factors to investigate their impact on the immune response and assess the cell viability of cancer cells. Our findings reveal that inhibiting DDX5 and DNA damage-related factors simultaneously in TNBC cells leads to a significantly greater decrease in cell viability than DDX5 knockdown alone. Through MTT assays using siRNA libraries related to DNA damage, we confirmed that when RAD51 and XRCC5 were knocked down along with DDX5, cell viability decreased by more than 20%. Furthermore, we noted an enhancement in innate immune activity and a more pronounced reduction in cell viability when simultaneously targeting the DNA damage-related factors alongside DDX5. In conclusion, our study identifies an augmented anticancer effect through the concurrent targeting of DDX5 and other critical factors. Citation Format: Hye-Ran Seo, Hwani Ryu, Jiyeon Ahn. Enhanced anticancer effects through synergistic targeting of DDX5 and DNA damage-related factors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr B029.