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

Area of Science:

• Hepatology
• Oncology
• Translational Medicine

Background:

• Hepatocellular carcinoma (HCC) is a rapidly growing and fatal cancer.
• Non-alcoholic steatohepatitis (NASH) is an increasingly recognized major cause of HCC.
• Studying NASH-to-HCC progression in humans is challenging, necessitating reliable preclinical models.

Purpose of the Study:

• To review the molecular mechanisms of NASH-related HCC.
• To critically evaluate existing mouse models for NASH-to-HCC progression.
• To compare human data with the MUP-uPA mouse model.

Main Methods:

• Literature review of NASH-related HCC molecular etiology.
• Critical evaluation of current NASH mouse models.
• Comparison of human transcriptomic and histopathological data with MUP-uPA mouse data.

Main Results:

• Many existing mouse models do not accurately mimic human NASH or reliably progress to HCC.
• The MUP-uPA mouse model demonstrates robust NASH-to-HCC progression.
• MUP-uPA mice are suitable for evaluating HCC immunotherapies.

Conclusions:

• Reliable preclinical models are crucial for understanding NASH-driven HCC pathogenesis.
• The MUP-uPA mouse model offers a valuable platform for NASH-related HCC research.
• Further research using validated models can advance therapeutic strategies for NASH-HCC.