The epigenetics changes associated with anthracyclines induced cardiotoxicity.

Advances in cancer treatment have significantly improved the survival of cancer patients, but unfortunately, many of these treatments also have long-term complications. Cancer treatmement related cardiotoxicities is becoming a significant clinical problem that a new discipline, Cardio-Oncology, was established to advance the cardiovascular care of growing cancer patient populations. Anthracyclines are a class of chemotherapeutic agents used to treat many cancers in adults and children. Their clinical use is limited by anthracycline-induced cardiotoxicity (AIC), which can lead to heart failure (HF). Early-onset cardiotoxicity appears within a year of treatment, while late-onset cardiotoxicity occurs more than one year and even up to decades after treatment completion. The pathophysiology of AIC was hypothesized to be caused by generation of reactive oxygen species (ROS) that lead to lipid peroxidation, defective mitochrondrial biogenesis, and DNA damage of the cardiomyocytes. The accumulation of anthracycline metabolites was also proposed to cause mitochondrial damage and the induction of cardiac cell apoptosis, which induces arrhythmias, contractile dysfunction, and cardiomyocyte death. This article will provide a general overview of cardiotoxicity focusing on the effect of anthracyclines and their epigenetic molecular mechanisms on cardiotoxicity.