Pharmacogenomic profiling of intra-tumor heterogeneity of liver cancer organoids

Inter- and intra-tumor heterogeneity is a major hurdle in primary liver cancer (PLC) precision therapy. In collaboration with Prof. Zhang Ning, we made a comprehensive investigation of a PLC biobank, consisting of 399 tumor organoids derived from 144 patients, which recapitulates histopathology and genomic landscape of parental tumors. Integrative analysis dissects PLC heterogeneity, regarding genomic/transcriptomic characteristics and sensitivity to seven clinically relevant drugs, as well as clinical associations. Pharmacogenomic analysis identifies and validates multi-gene expression signatures predicting drug response for better patient stratification. Furthermore, we reveal c-Jun as a major mediator of lenvatinib resistance through JNK and β-catenin signaling. Together, our study characterizes the landscape of PLC heterogeneity, develops predictive biomarker signatures, and identifies a lenvatinib-resistant mechanism for combination therapy.

Please read the article published in Cancer Cell (VOLUME 42, ISSUE 4, P535-551.E8, 2024) for the details.

Jianmin Wu
Center for Cancer Bioinformatics

ICGC-ARGO Scientific Planning Committee