Cancers, Vol. 12, Pages 2668: A Human Organoid Model of Aggressive Hepatoblastoma for Disease Modeling and Drug Testing
Cancers, Vol. 12, Pages 2668: A Human Organoid Model of Aggressive Hepatoblastoma for Disease Modeling and Drug Testing
Cancers doi: 10.3390/cancers12092668
Authors:
James A. Saltsman
William J. Hammond
Nicole J. C. Narayan
David Requena
Helmuth Gehart
Gadi Lalazar
Michael P. LaQuaglia
Hans Clevers
Sanford Simon
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 fro...
Source: Cancers - Category: Cancer & Oncology Authors: James A. Saltsman William J. Hammond Nicole J. C. Narayan David Requena Helmuth Gehart Gadi Lalazar Michael P. LaQuaglia Hans Clevers Sanford Simon Tags: Article Source Type: research
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