Cited by 1,471Cancer Cells and MetastasisHepatocellular Carcinoma Treatment and PrognosisLiver physiology and pathology

The DOI matches its Crossref record; 74 of the 74 references it cites were found in a registry or an index.

Human primary liver cancer–derived organoid cultures for disease modeling and drug screening

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Abstract

Human liver cancer research currently lacks in vitro models that can faithfully recapitulate the pathophysiology of the original tumor. We recently described a novel, near-physiological organoid culture system, wherein primary human healthy liver cells form long-term expanding organoids that retain liver tissue function and genetic stability. Here we extend this culture system to the propagation of primary liver cancer (PLC) organoids from three of the most common PLC subtypes: hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and combined HCC/CC (CHC) tumors. PLC-derived organoid cultures preserve the histological architecture, gene expression and genomic landscape of the original tumor, allowing for discrimination between different tumor tissues and subtypes, even after long-term expansion in culture in the same medium conditions. Xenograft studies demonstrate that the tumorogenic potential, histological features and metastatic properties of PLC-derived organoids are preserved in vivo. PLC-derived organoids are amenable for biomarker identification and drug-screening testing and led to the identification of the ERK inhibitor SCH772984 as a potential therapeutic agent for primary liver cancer. We thus demonstrate the wide-ranging biomedical utilities of PLC-derived organoid models in furthering the understanding of liver cancer biology and in developing personalized-medicine approaches for the disease.

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Metadata

Authors
Broutier, L., Mastrogiovanni, G., Verstegen, M. M., Francies, H. E., Gavarró, L. M., Bradshaw, C. R., Allen, G. E., Arnes-Benito, R., Sidorova, O., Gaspersz, M. P., Georgakopoulos, N., Koo, B.-K., Dietmann, S., Davies, S. E., Praseedom, R. K., Lieshout, R., IJzermans, J. N. M., Wigmore, S. J., Saeb-Parsy, K., Garnett, M. J., van der Laan, L. J., & Huch, M.
Affiliations
  • University of Cambridge (GB)
  • Wellcome/MRC Cambridge Stem Cell Institute (GB)
  • Erasmus MC (NL)
  • Wellcome Sanger Institute (GB)
  • Cambridge University Hospitals NHS Foundation Trust (GB)
  • Edinburgh Royal Infirmary (GB)
Corresponding author
Huch, Meritxell
Venue
Nature Medicine
Published
2017-11-13
Volume
23
Issue
12
Pages
1424-1435
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W2771057425
Cited by
1,471
References
74
Citations by year
2026: 151 · 2025: 163 · 2024: 203 · 2023: 182 · 2022: 204 · 2021: 243 · 2020: 151 · 2019: 99 · 2018: 73 · 2017: 2
FWCI
39.29
Type
journal article
Language
en
Open access
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
  • RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
  • HAL (submittedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo
Funders
  • Wellcome Trust (104151/Z/14/Z, C44943/A22536, 104151, 102696)
  • Cancer Research UK (102696, C44943/A22536, 22536)
  • University of Cambridge
  • European Commission (656193, 608180)
  • National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/R001162/1)
  • ZonMw
  • Cambridge University Hospitals
  • National Centre for the Replacement Refinement and Reduction of Animals in Research (NC/R001162/1)
  • Stand Up To Cancer (SU2C-AACRDT1213)
  • Horizon 2020 Framework Programme (MSCA-IF-2014)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
primary liver cancer, tumor organoids, hepatocellular carcinoma, cholangiocarcinoma, organoid culture, disease modeling, drug screening, xenografts, metastasis, biomarker discovery, ERK inhibitor, SCH772984, personalized medicine
MeSH terms
Animals, Antineoplastic Agents, Bile Duct Neoplasms, Drug Screening Assays, Antitumor, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Organoids, Tumor Cells, Cultured, Gene Expression Regulation, Neoplastic, Mice, SCID, Mice, Inbred NOD, Cholangiocarcinoma, Xenograft Model Antitumor Assays, Cell Proliferation, Mice, Precision Medicine, Transcriptome, Primary Cell Culture

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