Despite its serious cardiotoxicity, doxorubicin (DOX), has served as an effective antitumor agent for over 40 years.
DOX’s efficacy results from its ability to form a ternary complex with topoisomerase-II (Top2) and DNA, which triggers
cell death. The Top2α isoform, which is highly overexpressed in many cancer cells, is the primary target of DOX’s
antitumor activity. DOX’s cardiotoxicity has been attributed to its ability to generate reactive oxygen species (ROS), but the
failure of ROS scavengers to ameliorate DOX-dependent heart damage calls this hypothesis into question. This led Zhang
et al. [(2012) Nat. Med., 18, 1639] to investigate the role of Top2β, which is expressed in cardiomyocytes, in DOX-mediated
cardiotoxicity - 3 references