To extend our findings to an in vivo setting, we applied a previously established TKI-resistant model using immune-competent C57BL/6 N mice, in which TKI-resistant HCC tumors were developed from hydrodynamic tail vein injection of oncogenic plasmids expressing N-Ras and Akt and subsequent continuous treatment with sorafenib or lenvatinib (Fig. 6A and Suppl. Here, NRAS is linked to hepatocellular carcinoma.