4 years ago

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

Human primary liver cancer–derived organoid cultures for disease modeling and drug screening
Susan E Davies, Mathew J Garnett, Bon-Kyoung Koo, Nikitas Georgakopoulos, Luc JW van der Laan, Sabine Dietmann, Ruby Lieshout, Marcia P Gaspersz, Kourosh Saeb-Parsy, George E Allen, Lena Morrill Gavarró, Jan N M IJzermans, Raaj K Praseedom, Gianmarco Mastrogiovanni, Charles R Bradshaw, Hayley E Francies, Meritxell Huch, Robert Arnes-Benito, Laura Broutier, Stephen J Wigmore, Olga Sidorova, Monique MA Verstegen
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.

Publisher URL: https://www.nature.com/articles/nm.4438

DOI: 10.1038/nm.4438

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.