A study using the genome-wide CRISPR/Cas9 library screening system has also identified six genes, including dual specificity phosphatase 4 (DUSP4), as the genes associated with lenvatinib resistance, and the knockout of DUSP4 promotes cell proliferation and migration of HCC during lenvatinib treatment and activates ERK/MEK signaling at the phosphorylation level, inducing lenvatinib resistance [223]. Here, MAPK1 is linked to hepatocellular carcinoma.