In HCC cells with high levels of EGFR expression, treatment with lenvatinib results in feedback activation of the EGFR-P21 activated kinase 2 (PAK2)-extracellular signal-regulated kinase 5 (ERK5) signaling axis,25 while another study illustrates that HCC cells acquire lenvatinib resistance through activating the EGFR-signal transducer and activator of transcription 3 (STAT3)-ATP binding cassette subfamily B member 1 (ABCB1) pathway.26 Here, PAK2 is linked to hepatocellular carcinoma.