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Cell Metab. 2019 Jan 8;29(1):18-26. doi: 10.1016/j.cmet.2018.10.012. Epub 2018 Nov 15.

Preclinical Models for Studying NASH-Driven HCC: How Useful Are They?

Author information

1
Division of Diabetes & Metabolism, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia. Electronic address: m.febbraio@garvan.org.au.
2
Division of Diabetes & Metabolism, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
3
Department of Pharmacology, University of California San Diego, La Jolla, CA, USA.
4
Centre for Obesity Research & Education, Monash University, Clayton, VIC, Australia.
5
Department of Physiology, The University of Melbourne, Parkville, VIC, Australia.
6
Department of Pharmacology, University of California San Diego, La Jolla, CA, USA. Electronic address: karinoffice@ucsd.edu.

Abstract

Hepatocellular carcinoma (HCC) is one of the most fatal and fastest-growing cancers. Recently, non-alcoholic steatohepatitis (NASH) has been recognized as a major HCC catalyst. However, it is difficult to decipher the molecular mechanisms underlying the pathogenesis of NASH and understand how it progresses to HCC by studying humans. Progress in this field depends on the availability of reliable preclinical models amenable to genetic and functional analyses and exhibiting robust NASH-to-HCC progression. Although numerous mouse models of NASH have been described, many do not faithfully mimic the human disease and few reliably progress to HCC. Here, we review current literature on the molecular etiology of NASH-related HCC and critically evaluate existing mouse models and their suitability for studying this malignancy. We also compare human transcriptomic and histopathological profiles with data from MUP-uPA mice, a reliable model of NASH-driven HCC that has been useful for evaluation of HCC-targeting immunotherapies.

KEYWORDS:

RNA-seq; fatty liver; hepatocellular carcinoma; mouse models; non-alcoholic steatohepatitis; obesity

PMID:
30449681
PMCID:
PMC6326872
[Available on 2020-01-08]
DOI:
10.1016/j.cmet.2018.10.012

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