Novel Mechanisms of Anthracycline-Induced Cardiovascular Toxicity: A Focus on Thrombosis, Cardiac Atrophy, and Programmed Cell Death

Anthracycline antineoplastic agents such as doxorubicin are widely used and highly effective component of adjuvant chemotherapy for breast cancer and curative regimens for lymphomas, leukemias, and sarcomas. The primary dose-limiting adverse effect of anthracyclines is cardiotoxicity that typically manifests as cardiomyopathy and can progress to the potentially fatal clinical syndrome of heart failure. Decades of pre-clinical research have explicated the complex and multifaceted mechanisms of anthracycline-induced cardiotoxicity. It is well-established that oxidative stress contributes to the pathobiology and recent work has elucidated important central roles for direct mitochondrial injury and iron overload. Here we focus instead on emerging aspects of anthracycline-induced cardiotoxicity that may have received less attention in other recent reviews: thrombosis, myocardial atrophy, and non-apoptotic programmed cell death.