Mouse Models of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a major global health challenge and mouse models have been indispensable for elucidating its initiation, progression and therapeutic vulnerabilities. Three principal categories of murine HCC models have emerged: carcinogen-induced, genetically engineered and implantation-based systems. In carcinogen-induced models, agents such as diethylnitrosamine replicate the stepwise accumulation of DNA damage and fibrosis seen in human disease, allowing genomic and histological parallels to be drawn. Genetically engineered mouse models (GEMMs) leverage targeted mutations or transgene expression in oncogenes or tumour suppressors to dissect molecular drivers and test pathway-specific interventions. Implantation techniques range from ectopic xenografts of human or murine tumour cells to orthotopic engraftment within the liver, enabling evaluation of tumour-host interactions, immune responses and drug delivery. Emerging approaches, including hydrodynamic tail vein injection of oncogenic plasmids and transposon-mediated gene delivery, provide rapid and flexible platforms for modelling heterogeneity and tumour microenvironment influences. Across these models, key pathological features—fibrosis, steatosis and neoplastic lesion formation—can be tailored to reflect diverse aetiologies of human HCC. The integration of immunocompetent hosts and patient-derived xenografts further refines preclinical testing of immunotherapies and precision medicines, underscoring the translational significance of murine HCC systems.

Research from Nature Portfolio

Recent studies have demonstrated that well-characterised HCC cell lines retain the genomic and transcriptomic landscapes of primary human tumours when maintained at appropriate passages. Whole-genome analyses confirmed that driver mutations, copy-number alterations and oncogenic integrations remain stable during in vitro expansion, while global expression patterns mirror patient specimens. This fidelity supports the use of established cell lines as preclinical models for drug screening and mechanistic investigations, particularly in the context of precision medicine approaches targeting cancer driver genes and immune-evasion pathways.

Mouse Models of Hepatocellular Carcinoma publication trend

The graph below shows the total number of articles in mouse models of hepatocellular carcinoma across all publications each year (not limited to Nature Index journals).

Technical terms

Genetically engineered mouse model (GEMM): A mouse whose genome has been modified to carry or delete specific genes to study disease mechanisms.

Hydrodynamic tail vein injection: A rapid, large-volume intravenous method to deliver nucleic acids to the liver.

Neoplastic lesion: An area of abnormal tissue growth resulting from uncontrolled cell proliferation.

Tumour microenvironment: The cellular and molecular milieu surrounding a tumour, including stromal and immune components.

Carcinogen-induced model: A system in which chemical agents are administered to initiate tumour formation over time.

References

1. Oncogenic plasmid DNA and liver injury agent dictates liver cancer development in a mouse model. Clinical Science (2024).
2. Mutational landscape of a chemically-induced mouse model of liver cancer. Journal of Hepatology (2018).
3. Hepatocellular carcinoma cell lines retain the genomic and transcriptomic landscapes of primary human cancers. Scientific Reports (2016).
4. A novel spontaneous hepatocellular carcinoma mouse model for studying T-cell exhaustion in the tumor microenvironment. Journal for ImmunoTherapy of Cancer (2018).