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Liu et al. Hepatoma Res 2020;6:7 I http://dx.doi.org/10.20517/2394-5079.2019.39 Page 13 of 16

recapitulate the histological architecture, expression profile, genomic landscape and in vivo tumourigenesis
[37]
of the parental tumour, even after long-term (> 1 year) expansion in culture . Furthermore, tumouroids
could be established within 2-3 months after isolation. Therefore, tumouroids fulfil many of the criteria for
a reliable cancer model which animal models could not and may represent a promising advancement for
understanding tumour biology and drug efficacy testing in future studies of HCC. However, they currently
lack the human immune and stromal microenvironment that is thought to be crucial in understanding
tumour progression and response to treatment, particularly immune-based therapies.

CONCLUSION
Alcoholic and metabolic liver diseases will be major contributors to HCC burden in the future. Many
aspects of human HCC development and progression remain unknown, negatively impacting therapeutic
advancement. Animal models play a crucial role in improving our understanding of human HCC and
developing novel therapeutic strategies. Currently, no animal model can faithfully replicate the complexity
of the cancer and its background liver disease but mere aspects of it with varying degrees of technical
demand. The careful combination of different animal models and use of novel technologies such as human
organoids may help bridge this gap in the future. For the time being, the use of HCC mouse models needs
to be tailored to specific experimental hypothesis or clinical testing.

DECLARATIONS
Authors’ contributions
Acquisition, analysis and interpretation of data, drafting of the article, critical revision of the article: Liu K,
Chen J, McCaughan GW
All authors have read and approved the final version.

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2020.

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