Loss of NF1 reactivates PI3K/AKT as well as MAPK/ERK pathways in HCC cells inhibited by Lenvatinib, loss of DUSP9 activates MAPK/ERK pathway and induces phosphorylation of AKT and ERK to induce Lenvatinib resistance (Lu et al., 2021). This evidence concerns the gene EPHB2 and hepatocellular carcinoma.