In hepatocellular carcinoma, Notch3 rather than Notch1 contributed to the doxorubicin resistance, and the advantage of combining anti-Notch3 treatment and doxorubicin for DNA damage and apoptosis induction was related to increased p53 expression and failed to be beneficial in p53-/-, consistent with the known role of p53 inactivation in conferring HCC resistance to doxorubicin [502,503]. This evidence concerns the gene TP53 and hepatocellular carcinoma.