{Reference Type}: Journal Article
{Title}: Integrated characterization of hepatobiliary tumor organoids provides a potential landscape of pharmacogenomic interactions.
{Author}: Zhu Y;Tang S;Yuan Q;Fu J;He J;Liu Z;Zhao X;Li Y;Zhao Y;Zhang Y;Zhang X;Zhang Y;Zhu Y;Wang W;Zheng B;Wu R;Wu T;Yang S;Qiu X;Shen S;Hu J;Chen L;Wang Y;Wang H;Gao D;Chen L;
{Journal}: Cell Rep Med
{Volume}: 5
{Issue}: 2
{Year}: 2024 Feb 20
{Factor}: 16.988
{DOI}: 10.1016/j.xcrm.2023.101375
{Abstract}: Despite considerable efforts to identify human liver cancer genomic alterations that might unveil druggable targets, the systematic translation of multiomics data remains challenging. Here, we report success in long-term culture of 64 patient-derived hepatobiliary tumor organoids (PDHOs) from a Chinese population. A divergent response to 265 metabolism- and epigenetics-related chemicals and 36 anti-cancer drugs is observed. Integration of the whole genome, transcriptome, chromatin accessibility profiles, and drug sensitivity results of 64 clinically relevant drugs defines over 32,000 genome-drug interactions. RUNX1 promoter mutation is associated with an increase in chromatin accessibility and a concomitant gene expression increase, promoting a cluster of drugs preferentially sensitive in hepatobiliary tumors. These results not only provide an annotated PDHO biobank of human liver cancer but also suggest a systematic approach for obtaining a comprehensive understanding of the gene-regulatory network of liver cancer, advancing the applications of potential personalized medicine.