Establishment of Primary Liver Cancer Organoids and Application on Sorafenib Resistance

Current in vitro models of primary liver cancer fail to recapitulate the key characteristics of original cancer. We construct the long-term organoids culture from tumor tissue of primary liver cancer (PLC) patients with varieties of subtypes. PLC organoids retain the histopathological features of originating tumor. Organoids transplantation proved that the tumorogenic potential and histological characteristics of PLC organoids are well preserved in vivo. PLC organoids are amenable for preclinical drug screening test and identification of mammalian target of rapamycin (mTOR) inhibitor compound as a potential therapeutic treatment for PLC. Besides, we also establish sorafenib-resistant hepatocellular carcinoma (HCC) organoids to clarify the mechanisms that drive resistance. In conclusion, PLC organoids models provide a platform for drug development for PLC and theoretical basis for HCC resistance. Paired sorafenib-resistant and -sensitive tumor-derived organoids from 4 HCC patients