Human Primary Liver Cancer -derived Organoid Cultures for disease modelling and drug screening

By L. Broutier, Gianmarco Mastrogiovanni, M. Verstegen, Hayley E. Francies, Lena Morrill Gavarró, C. Bradshaw, George E. Allen, Robert Arnes-Benito, O. Sidorova, M. Gaspersz and 12 more. Nature Medicine, 2017

1,256 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Hepatology

View Paper: https://www.semanticscholar.org/paper/84bc2d037342f3904a2fc4c0bf25f09905f5d72c

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In Cancer Research

Citations in the corpus

A Patient-Derived Glioblastoma Organoid Model and Biobank Recapitulates Inter- and Intra-tumoral Heterogeneity. (2019, background): “Organoids have since been applied to model various cancers, including pancreatic, prostate, liver, breast, bladder, ovarian, and gastrointestinal cancers (Boj et al., 2015; Broutier et al., 2017; Gao et al., 2014; Kopper et al., 2019; Lee et al., 2018; Sachs et al., 2018; Yan et al., 2018).”
Organoids (2022, neutral): “Adapted from ref.(131), Springer Nature Limited.”