TP53 and heart failure: While topoisomerase 2β (expressed mostly in proliferating cells) is considered as the primary target of DOX in tumor cells, topoisomerase 2α (expressed by quiescent cells) has been made responsible for suppression of antioxidant enzyme expression, inhibition of mitochondrial biogenesis, and activation of p53 and p53-mediated apoptosis with all of these cellular events implicated in DOX-induced heart failure [25].