A Human Organoid Model of Aggressive Hepatoblastoma for Disease Modeling and Drug Testing
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/9/2668 |
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| author | James A. Saltsman William J. Hammond Nicole J. C. Narayan David Requena Helmuth Gehart Gadi Lalazar Michael P. LaQuaglia Hans Clevers Sanford Simon |
| author_facet | James A. Saltsman William J. Hammond Nicole J. C. Narayan David Requena Helmuth Gehart Gadi Lalazar Michael P. LaQuaglia Hans Clevers Sanford Simon |
| author_sort | James A. Saltsman |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T16:14:07Z |
| format | Article |
| id | doaj.art-f50f8ff89fc6433eb1f67e53a4ce7813 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T16:14:07Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f50f8ff89fc6433eb1f67e53a4ce78132023-11-20T14:14:19ZengMDPI AGCancers2072-66942020-09-01129266810.3390/cancers12092668A Human Organoid Model of Aggressive Hepatoblastoma for Disease Modeling and Drug TestingJames A. Saltsman0William J. Hammond1Nicole J. C. Narayan2David Requena3Helmuth Gehart4Gadi Lalazar5Michael P. LaQuaglia6Hans Clevers7Sanford Simon8Laboratory of Cellular Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USALaboratory of Cellular Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USALaboratory of Cellular Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USALaboratory of Cellular Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USAHubrecht Institute, KNAW and University Medical Center Utrecht, 3584CT Utrecht, The NetherlandsLaboratory of Cellular Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USAPediatric Surgery Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USAHubrecht Institute, KNAW and University Medical Center Utrecht, 3584CT Utrecht, The NetherlandsLaboratory of Cellular Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USAHepatoblastoma 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.https://www.mdpi.com/2072-6694/12/9/2668pediatricsoncologypediatric oncologypediatric solid tumorliver cancerhepatoblastoma |
| spellingShingle | James A. Saltsman William J. Hammond Nicole J. C. Narayan David Requena Helmuth Gehart Gadi Lalazar Michael P. LaQuaglia Hans Clevers Sanford Simon A Human Organoid Model of Aggressive Hepatoblastoma for Disease Modeling and Drug Testing Cancers pediatrics oncology pediatric oncology pediatric solid tumor liver cancer hepatoblastoma |
| title | A Human Organoid Model of Aggressive Hepatoblastoma for Disease Modeling and Drug Testing |
| title_full | A Human Organoid Model of Aggressive Hepatoblastoma for Disease Modeling and Drug Testing |
| title_fullStr | A Human Organoid Model of Aggressive Hepatoblastoma for Disease Modeling and Drug Testing |
| title_full_unstemmed | A Human Organoid Model of Aggressive Hepatoblastoma for Disease Modeling and Drug Testing |
| title_short | A Human Organoid Model of Aggressive Hepatoblastoma for Disease Modeling and Drug Testing |
| title_sort | human organoid model of aggressive hepatoblastoma for disease modeling and drug testing |
| topic | pediatrics oncology pediatric oncology pediatric solid tumor liver cancer hepatoblastoma |
| url | https://www.mdpi.com/2072-6694/12/9/2668 |
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