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.
journal_name
Nat Medjournal_title
Nature medicineauthors
Broutier L,Mastrogiovanni G,Verstegen MM,Francies HE,Gavarró LM,Bradshaw CR,Allen GE,Arnes-Benito R,Sidorova O,Gaspersz MP,Georgakopoulos N,Koo BK,Dietmann S,Davies SE,Praseedom RK,Lieshout R,IJzermans JNM,Wigmore SJ,doi
10.1038/nm.4438subject
Has Abstractpub_date
2017-12-01 00:00:00pages
1424-1435issue
12eissn
1078-8956issn
1546-170Xpii
nm.4438journal_volume
23pub_type
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