Organoid Models of Human Liver Cancers Derived from Tumor Needle Biopsies

Summary Hepatocellular carcinoma ( HCC) is the most common primary liver cancerand the second most frequent causeof cancer-related mortality worldwide. The multikinase inhibitor sorafenibis 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 organoidcultures from tumor needle biopsies of HCCpatients with various etiologies and tumor stages. HCC organoidsretain the morphology as well as the expression pattern of HCC tumor markersand preserve the genetic heterogeneity of the originating tumors. In a proof-of-principle study, we show that liver cancer organoidscan be used to test sensitivityto sorafenib. In conclusion, organoidmodels can be derived from needle biopsies of liver cancersand provide a tool for developing tailored therapies.