In Vivo and In Vitro Models of Hepatocellular Carcinoma: Current Strategies for Translational Modeling

Abstract

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer-related death globally. HCC is a complex multistep disease and usually emerges in the setting of chronic liver diseases. The molecular pathogenesis of HCC varies according to the etiology, mainly caused by chronic hepatitis B and C virus infections, chronic alcohol consumption, aflatoxin-contaminated food, and non-alcoholic fatty liver disease associated with metabolic syndrome or diabetes mellitus. The establishment of HCC models has become essential for both basic and translational research to improve our understanding of the pathophysiology and unravel new molecular drivers of this disease. The ideal model should recapitulate key events observed during hepatocarcinogenesis and HCC progression in view of establishing effective diagnostic and therapeutic strategies to be translated into clinical practice. Despite considerable efforts currently devoted to liver cancer research, only a few anti-HCC drugs are available, and patient prognosis and survival are still poor. The present paper provides a state-of-the-art overview of in vivo and in vitro models used for translational modeling of HCC with a specific focus on their key molecular hallmarks.

Liver-specific deletion of miR-181ab1 reduces liver tumour progression via upregulation of CBX7

“…The DEN model lacks some vital features in human liver cancer development, such as chronic liver inflammation and liver fibrosis. Thus, additional animal models, especially models with chronic liver inflammation and liver fibrosis, may be needed to further explore the miR-181/CBX7 axis in hepatocarcinogenesis [ 65 – 67 ]. Second, the miR-181/CBX7 axis might play a role in some human HCCs only, as only one-third of human HCCs show high miR-181 and low CBX7 expressions [ 4 ].…”

High expression of the ANXA3 gene promotes immune infiltration and improves tumor prognosis in ovarian serous carcinoma using bioinformatics analyses

“…To date, ANXA3 has been found to not only maintain genomic integrity and facilitate cell proliferation and differentiation but also contributes to tumor initiation and growth. We synthesized the relevant literature and found that that ANXA3 expression was dysregulated in a large number of tumor populations, such as bladder urothelial carcinoma ( 23 ), BRCA ( 17 ), CHOL ( 16 ), COAD ( 24 ), esophageal carcinoma ( 25 ), head and neck squamous cell carcinoma ( 26 ), kidney chromophobe ( 27 ), kidney renal papillary cell carcinoma ( 28 ), hepatocellular carcinoma ( 29 ), LUAD ( 30 ), LUSC ( 31 ), pancreatic adenocarcinoma ( 32 ), PRAD ( 33 ), READ ( 34 ), stomach adenocarcinoma ( 25 ), thyroid carcinoma ( 35 ), and uterine corpus endometrial carcinoma ( 13 ). In this study, an increased ANXA3 expression was associated with a favorable prognosis, suggesting that ANXA3 might play a pivotal role in decreasing cancer risk in patients with OV.…”

G × E interactions as a basis for toxicological uncertainty

“…This assumption is in line with partially significant differences between the model systems. In some areas of toxicology, one animal species is 60% predictive of another one (Smirnova et al 2018 ), and even strains of mice may show sensitivity differences to carcinogens by > 100-fold (Diwan et al 1986 ; Romualdo et al 2021 ). Understanding the underlying G × E effects is important for the selection of models with the best translational value in toxicology or in disease biology.…”