Title
A human organoid model of aggressive hepatoblastoma for disease modeling and drug testing
Date Issued
01 September 2020
Access level
metadata only access
Resource Type
research article
Author(s)
Saltsman J.A.
Hammond W.J.
Narayan N.J.C.
Gehart H.
Lalazar G.
Laquaglia M.P.
Clevers H.
Simon S.
The Rockefeller University
Publisher(s)
MDPI AG
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.
Start page
1
End page
18
Volume
12
Issue
9
Language
English
OCDE Knowledge area
Tecnología médica de laboratorio (análisis de muestras, tecnologías para el diagnóstico)
Tecnologías que implican la manipulación de células, tejidos, órganos o todo el organismo
Subjects
Scopus EID
2-s2.0-85091049888
Source
Cancers
ISSN of the container
20726694
Sources of information:
Directorio de Producción Científica
Scopus