Genetically Engineered Mouse Models for Liver Cancer

Abstract

Liver cancer is the fourth leading cause of cancer-related death globally, accounting for approximately 800,000 deaths annually. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, comprising approximately 80% of cases. Murine models of HCC, such as chemically-induced models, xenograft models, and genetically engineered mouse (GEM) models, are valuable tools to reproduce human HCC biopathology and biochemistry. These models can be used to identify potential biomarkers, evaluate potential novel therapeutic drugs in pre-clinical trials, and develop molecular target therapies. Considering molecular target therapies, a novel approach has been developed to create genetically engineered murine models for HCC, employing hydrodynamics-based transfection (HT). The HT method, coupled with the Sleeping Beauty transposon system or the CRISPR/Cas9 genome editing tool, has been used to rapidly and cost-effectively produce a variety of HCC models containing diverse oncogenes or inactivated tumor suppressor genes. The versatility of these models is expected to broaden our knowledge of the genetic mechanisms underlying human hepatocarcinogenesis, allowing the study of premalignant and malignant liver lesions and the evaluation of new therapeutic strategies. Here, we review recent advances in GEM models of HCC with an emphasis on new technologies.