Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Despite new treatment approvals, the prognosis of patients with advanced HCC remains poor. Gene expression profiling combined with single cell RNA sequencing (scRNASeq) and spatial transcriptomics has markedly advanced our understanding of the disease biology of liver disease progressing to cancer. Here we developed novel patient-derived cell-based systems to model the tumor biology and its microenvironment. Using gene expression profiling combined with scRNA and spatial transcriptomics we identified novel targets and compounds to prevent and treat liver cancer with completed preclinical proof-of-concept. The development of novel therapeutic approaches provides an opportunity to improve the dismal outcome of patients with liver cancer. |