[P006] Poster

1:00 PM - 1:50 PM JST(4:00 AM - 4:50 AM UTC)

[P03-422] Organoid-Based Drug Repurposing Identifies Dual-Action Therapeutics Targeting HBV Replication and HBV-Associated Hepatocellular Carcinoma

○GEONWOO KIM¹, JAESU MOON² (1. Chungnam National University (Korea), 2. Korea Research Institute of Chemical Technology (Korea))

Keywords:

Liver Organoid,Hepatitis B virus,Hepatocellular Carcinoma

Hepatitis B virus (HBV) infection remains a major global health burden, contributing to chronic liver disease and hepatocellular carcinoma (HCC), one of the leading causes of cancer-related mortality worldwide. Despite the availability of nucleos(t)ide analogues, complete viral eradication is limited by the persistence of covalently closed circular DNA (cccDNA), while therapeutic options for HCC are constrained by drug resistance and limited efficacy, particularly in HBV-associated cases. To address these challenges, we established a physiologically relevant screening platform integrating patient-derived hepatocyte organoids that recapitulate both HBV infection and tumorigenic features of HCC. This organoid-based system enables simultaneous evaluation of antiviral activity and anti-tumor efficacy within a clinically relevant microenvironment, overcoming limitations of conventional 2D cell models. Using this platform, we performed a high-throughput drug repurposing screen of 3,200 FDA-approved compounds to identify candidates with dual therapeutic potential. From this screening, 39 small molecules significantly inhibited HCC organoid growth, indicating robust anti-proliferative activity. Notably, among these candidates, 3 compounds also demonstrated potent suppression of HBV replication, suggesting a dual mechanism targeting both viral persistence and tumor progression. Mechanistically, these findings highlight the feasibility of leveraging existing chemical space to identify compounds capable of modulating host-virus interactions and oncogenic pathways simultaneously. Furthermore, this study underscores the utility of organoid-based platforms in bridging tissue-level disease modeling with compound screening, enabling more predictive evaluation of therapeutic efficacy. Collectively, our results provide a proof-of-concept for organoid-guided drug repurposing strategies to develop dual-action therapeutics targeting both HBV replication and HBV-associated hepatocarcinogenesis, offering a promising translational approach for improving clinical outcomes in HBV-related HCC.