One possible explanation for treatment failure could be that mutations of the kinase domain of EGFR do not play a significant role in the tumorigenesis of HCC as activating mutations have not been reported in human HCCs [196,197], whereas for example for non-small cell lung carcinomas the treatment response to gefitinib correlated with an activating mutation in the kinase domain [180]. Here, EGFR is linked to hepatocellular carcinoma.