Anthracycline-induced cardiomyopathy: cellular and molecular mechanisms.

ABSTRACT

Despite the known risk of cardiotoxicity, anthracyclines are widely prescribed chemotherapeutic agents. They are broadly characterized as being a robust effector of cellular apoptosis in rapidly proliferating cells through its actions in the nucleus and formation of reactive oxygen species (ROS). And, despite the early use of dexrazoxane, no effective treatment strategy has emerged to prevent the development of cardiomyopathy, despite decades of study, suggesting that much more insight into the underlying mechanism of the development of cardiomyopathy is needed. In this review, we detail the specific intracellular activities of anthracyclines, from the cell membrane to the sarcoplasmic reticulum, and highlight potential therapeutic windows that represent the forefront of research into the underlying causes of anthracycline-induced cardiomyopathy.