A human organoid model of aggressive hepatoblastoma for disease modeling and drug testing Journal Article


Authors: Saltsman, J. A.; Hammond, W. J.; Narayan, N. J. C.; Requena, D.; Gehart, H.; Lalazar, G.; LaQuaglia, M. P.; Clevers, H.; Simon, S.
Article Title: A human organoid model of aggressive hepatoblastoma for disease modeling and drug testing
Abstract: Hepatoblastoma is the most common childhood liver cancer. Although survival has improved significantly over the past few decades, there remains a group of children with aggressive disease who do not respond to current treatment regimens. There is a critical need for novel models to study aggressive hepatoblastoma as research to find new treatments is hampered by the small number of laboratory models of the disease. Organoids have emerged as robust models for many diseases, including cancer. We have generated and characterized a novel organoid model of aggressive hepatoblastoma directly from freshly resected patient tumors as a proof of concept for this approach. Hepatoblastoma tumor organoids recapitulate the key elements of patient tumors, including tumor architecture, mutational profile, gene expression patterns, and features of Wnt/β-catenin signaling that are hallmarks of hepatoblastoma pathophysiology. Tumor organoids were successfully used alongside non-tumor liver organoids from the same patient to perform a drug screen using twelve candidate compounds. One drug, JQ1, demonstrated increased destruction of liver organoids from hepatoblastoma tumor tissue relative to organoids from the adjacent non-tumor liver. Our findings suggest that hepatoblastoma organoids could be used for a variety of applications and have the potential to improve treatment options for the subset of hepatoblastoma patients who do not respond to existing treatments. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Keywords: oncology; liver cancer; pediatric oncology; pediatrics; sequencing; hepatoblastoma; organoids; pediatric solid tumor; 3-d culture
Journal Title: Cancers
Volume: 12
Issue: 9
ISSN: 2072-6694
Publisher: MDPI  
Date Published: 2020-09-01
Start Page: 2668
Language: English
DOI: 10.3390/cancers12092668
PROVIDER: scopus
PUBMED: 32962010
PMCID: PMC7563272
DOI/URL:
Notes: Article -- Export Date: 1 October 2020 -- Source: Scopus
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  1. William Joseph Hammond
    11 Hammond