Preclinical models of non-alcoholic steatohepatitis leading to hepatocellular carcinoma. (January 2023)

• Record Type: Journal Article
• Authors: Green, Christopher D.; Spiegel, Sarah
• Is Part Of: Advances in biological regulation. Volume 87(2023)
• Publication Date: 2023-01
• Subjects: Non-alcoholic fatty liver disease -- Non-alcoholic steatohepatitis -- Liver fibrosis -- Hepatocellular carcinoma -- Liver cancer; AOX acetyl-coenzyme A oxidase -- ER endoplasmic reticulum -- GTT glucose tolerance test -- NAFLD non-alcoholic fatty liver disease -- NASH non-alcoholic steatohepatitis -- HCC hepatocellular carcinoma -- HFD high fat diet -- PTEN phosphatase and tensin homolog 10 -- SREBP1 sterol regulatory element binding protein 1 -- SW sugar water -- STZ streptozotocin; Cellular control mechanisms -- Periodicals; Biological control systems -- Periodicals; Molecular biology -- Periodicals; Periodicals; 571.74
• DOI: 10.1016/j.jbior.2022.100925
• Languages: English
• ISSNs: 2212-4926

Abstract

Abstract: Hepatocellular carcinoma (HCC) is the third leading cause of cancer related deaths worldwide and its incidence is increasing due to endemic obesity and the growing burden of non-alcoholic steatohepatitis (NASH) associated liver cancer. Although much is known about the clinical and histological pathology of NASH-driven HCC in humans, its etiology remains unclear and there is a lack of reliable biomarkers and limited effective therapies. Progress has been hampered by the scarcity of standardized animal models that recapitulate the gradual progression of NASH towards HCC observed in humans. Here we review existing mouse models and their suitability for studying NASH-driven HCC with special emphasis on a preclinical model that we recently developed that faithfully mimics all the clinical endpoints of progression of the human disease. Moreover, it is highly translatable, allows the use of gene-targeted mice, and is suitable for gaining knowledge of how NASH progresses to HCC and development of new targets for treatment.