Organoid Models of Human Liver Cancers Derived from Tumor Needle Biopsies

Sandro Nuciforo; Isabel Fofana; Matthias S Matter; Tanja Blumer; Diego Calabrese; Tujana Boldanova; Salvatore Piscuoglio; Stefan Wieland; Femke Ringnalda; Gerald Schwank; Luigi M Terracciano; Charlotte K Y Ng; Markus H Heim

doi:10.1016/j.celrep.2018.07.001

Organoid Models of Human Liver Cancers Derived from Tumor Needle Biopsies

Cell Rep. 2018 Jul 31;24(5):1363-1376. doi: 10.1016/j.celrep.2018.07.001.

Affiliations

¹ Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
² Institute of Pathology, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
³ Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland; Clinic of Gastroenterology and Hepatology, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
⁴ Institute of Molecular Health Sciences, ETH Zurich, Otto-Stern-Weg 7, HPL, 8093 Zürich, Switzerland.
⁵ Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland; Institute of Pathology, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
⁶ Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland; Clinic of Gastroenterology and Hepatology, University Hospital Basel, University of Basel, 4031 Basel, Switzerland. Electronic address: [email protected].

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the second most frequent cause of cancer-related mortality worldwide. The multikinase inhibitor sorafenib is the only treatment option for advanced HCC. Due to tumor heterogeneity, its efficacy greatly varies between patients and is limited due to adverse effects and drug resistance. Current in vitro models fail to recapitulate key features of HCCs. We report the generation of long-term organoid cultures from tumor needle biopsies of HCC patients with various etiologies and tumor stages. HCC organoids retain the morphology as well as the expression pattern of HCC tumor markers and preserve the genetic heterogeneity of the originating tumors. In a proof-of-principle study, we show that liver cancer organoids can be used to test sensitivity to sorafenib. In conclusion, organoid models can be derived from needle biopsies of liver cancers and provide a tool for developing tailored therapies.

Keywords: Biobank; cholangiocellular carcinoma; drug response; genetic heterogeneity; hepatocellular carcinoma; liver; needle biopsy; patient-derived organoids; patient-derived xenografts.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Animals
Carcinoma, Hepatocellular / pathology*
Cells, Cultured
Female
Humans
Liver Neoplasms / pathology*
Male
Mice
Middle Aged
Organoids / pathology*
Tissue Culture Techniques / methods