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Integrated characterization of hepatobiliary tumor organoids provides a potential landscape of pharmacogenomic interactions
- Source :
- Cell Reports Medicine; February 2024, Vol. 5 Issue: 2
- Publication Year :
- 2024
-
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.
Details
- Language :
- English
- ISSN :
- 26663791
- Volume :
- 5
- Issue :
- 2
- Database :
- Supplemental Index
- Journal :
- Cell Reports Medicine
- Publication Type :
- Periodical
- Accession number :
- ejs65513493
- Full Text :
- https://doi.org/10.1016/j.xcrm.2023.101375