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

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.

Type Journal
ISBN 1932-7420 (Electronic) 1550-4131 (Linking)
Authors Febbraio, M. A.; Reibe, S.; Shalapour, S.; Ooi, G. J.; Watt, M. J.; Karin, M.
Responsible Garvan Author (missing name)
Publisher Name Cell Metabolism
Published Date 2019-01-01
Published Volume 29
Published Issue 1
Published Pages 18-26
Status Published in-print
DOI 10.1016/j.cmet.2018.10.012
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/30449681