In addition, doxorubicin induces acute and chronic cardiomyocyte apoptosis leading to cardiac dysfunction, cardiomyopathy, and eventually to severe heart failure and death due to activation of ERK1/2-mediated P53 and ROS-mediated MAPK and NF-κB, as well as P53-dependent PUMA upregulation signaling [61, 65]. This evidence concerns the gene TP53 and heart failure.