Image of Emerging Pathway of Doxorubin Cardiotoxicity.
Doxorubicin (DOX) is among the oldest and most-used chemotherapeutics. However, its use is limited by a cumulative dose that leads to cardiotoxicity. DOX is an anthracycline quinone that is known to produce reactive oxygen species (ROS). Although ROS play a function in mediating cardiotoxicity, alternative mechanisms that govern its specific cardiotoxicity remain elusive. This is exemplified by the fact that 5-iminodaunorubicin (5-IDN) and zorubicin (ZRN) are relatively noncardiotoxic analogues, even though ZRN forms ROS as efficiently as DOX and 5-IDN produces many fewer ROS.(1) Having a better understanding of the mechanisms underlying DOX cardiotoxicity will be beneficial in the development of efficacious and nontoxic analogues of DOX for cancer chemotherapy.