Hepatoblastoma Cell Lines: Past, Present and Future.

Area of Science:

• Pediatric Oncology
• Cancer Cell Biology
• Genetics and Genomics

Background:

• Hepatoblastoma (HB) is the most common pediatric liver cancer, with limited treatment options for advanced or recurrent cases.
• Current HB research is hindered by a lack of diverse, representative cell lines, especially for common molecular subtypes.
• Pediatric cancer therapies can lead to significant long-term health issues in young patients.

Purpose of the Study:

• To highlight the utility of immortalized cell lines for drug screening and identifying novel therapeutic targets in hepatoblastoma.
• To introduce novel murine hepatoblastoma models that recapitulate key human molecular subtypes.
• To address the critical need for better in vitro models in pediatric liver cancer research.

Main Methods:

• Generation of immortalized murine hepatoblastoma cell lines driven by common oncogenes/tumor suppressors (β-catenin, YAP, NRF2, MYC).
• Characterization of these cell lines for molecular and phenotypic resemblance to human hepatoblastoma.
• Utilizing CRISPR-based screens for target identification and studying cell trans-differentiation.

Main Results:

• Five distinct groups of murine HB cell lines were established, reflecting common human HB oncogenic drivers.
• These models exhibit molecular signatures and attributes similar to human hepatoblastoma.
• Demonstrated utility in identifying therapeutic targets and revealing HB cell plasticity (trans-differentiation into endothelial cells).

Conclusions:

• Novel murine hepatoblastoma models offer valuable tools for advancing pediatric liver cancer research.
• These models can facilitate drug screening, target identification, and understanding tumor biology.
• Future development may lead to bespoke immortalized human hepatoblastoma cell lines.