Title
Human liver organoids for disease modeling of fibrolamellar carcinoma
Date Issued
09 August 2022
Access level
open access
Resource Type
journal article
Author(s)
Narayan N.J.C.
Lalazar G.
Ramos-Espiritu L.
Ng D.
Levin S.
Shebl B.
Wang R.
Hammond W.J.
Saltsman J.A.
Gehart H.
Torbenson M.S.
Clevers H.
LaQuaglia M.P.
Simon S.M.
The Rockefeller University
Publisher(s)
Cell Press
Abstract
Fibrolamellar carcinoma (FLC) is a rare, often lethal, liver cancer affecting adolescents and young adults, for which there are no approved therapeutics. The development of therapeutics is hampered by a lack of in vitro models. Organoids have shown utility as a model system for studying many diseases. In this study, tumor tissue and the adjacent non-tumor liver were obtained at the time of surgery. The tissue was dissociated and grown as organoids. We developed 21 patient-derived organoid lines: 12 from metastases, three from the liver tumor and six from adjacent non-tumor liver. These patient-derived FLC organoids recapitulate the histologic morphology, immunohistochemistry, and transcriptome of the patient tumor. Patient-derived FLC organoids were used in a preliminary high-throughput drug screen to show proof of concept for the identification of therapeutics. This model system has the potential to improve our understanding of this rare cancer and holds significant promise for drug testing and development.
Start page
1874
End page
1888
Volume
17
Issue
8
Language
English
OCDE Knowledge area
OncologÃa
PatologÃa
GastroenterologÃa, HepatologÃa
Subjects
Scopus EID
2-s2.0-85135689782
PubMed ID
Source
Stem Cell Reports
ISSN of the container
22136711
Sponsor(s)
We are grateful for the support of The Rally Foundation for Childhood Cancer Research grants and the Truth 365 519023 and 401943 (W.J.H., J.A.S., S.M.S.), the support of the NIH / NCI grant 1P50CA210964 and 1U54CA243126 (S.M.S.), NIH / NCI P30CA008748 (N.J.C., M.P.L.), NIH / NCATS grants Clinical and Translation Science Awards UL1TR001866 (G.L., S.M.S.) and UL1TR000043 (W.J.H. and SMS). We acknowledge the use of the Integrated Genomics Operation Core, funded by the NCI Cancer Center Support Grant (CCSG, P30 CA08748 ), Cycle for Survival, and the Marie-Josée and Henry R. Kravis Center for Molecular Oncology. We would like to acknowledge Irina Linkov of the MSKCC Pathology Core Facility for help. We are also grateful for the support and contributions of the patients and caregivers.
Sources of information:
Directorio de Producción CientÃfica
Scopus