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BMC Cancer
Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Hepatitis B | Review

HBV-related hepatocarcinogenesis: the role of signalling pathways and innovative ex vivo research models

Authors: Joseph Torresi, Bang Manh Tran, Dale Christiansen, Linda Earnest-Silveira, Renate Hilda Marianne Schwab, Elizabeth Vincan

Published in: BMC Cancer | Issue 1/2019

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Abstract

Background

Hepatitis B virus (HBV) is the leading cause of liver cancer, but the mechanisms by which HBV causes liver cancer are poorly understood and chemotherapeutic strategies to cure liver cancer are not available. A better understanding of how HBV requisitions cellular components in the liver will identify novel therapeutic targets for HBV associated hepatocellular carcinoma (HCC).

Main body

The development of HCC involves deregulation in several cellular signalling pathways including Wnt/FZD/β-catenin, PI3K/Akt/mTOR, IRS1/IGF, and Ras/Raf/MAPK. HBV is known to dysregulate several hepatocyte pathways and cell cycle regulation resulting in HCC development. A number of these HBV induced changes are also mediated through the Wnt/FZD/β-catenin pathway. The lack of a suitable human liver model for the study of HBV has hampered research into understanding pathogenesis of HBV. Primary human hepatocytes provide one option; however, these cells are prone to losing their hepatic functionality and their ability to support HBV replication. Another approach involves induced-pluripotent stem (iPS) cell-derived hepatocytes. However, iPS technology relies on retroviruses or lentiviruses for effective gene delivery and pose the risk of activating a range of oncogenes. Liver organoids developed from patient-derived liver tissues provide a significant advance in HCC research. Liver organoids retain the characteristics of their original tissue, undergo unlimited expansion, can be differentiated into mature hepatocytes and are susceptible to natural infection with HBV.

Conclusion

By utilizing new ex vivo techniques like liver organoids it will become possible to develop improved and personalized therapeutic approaches that will improve HCC outcomes and potentially lead to a cure for HBV.
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Metadata
Title
HBV-related hepatocarcinogenesis: the role of signalling pathways and innovative ex vivo research models
Authors
Joseph Torresi
Bang Manh Tran
Dale Christiansen
Linda Earnest-Silveira
Renate Hilda Marianne Schwab
Elizabeth Vincan
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-5916-6

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