Mitochondria and doxorubicin-induced cardiomyopathy. A complex interplay

Cardiotoxicity has emerged as a major side effect of doxorubicin (DOX) treatment,affecting nearly 30% of patients within 5 years after chemotherapy. Heart failure is the first non-cancer cause of death in DOX-treated patients. Although many different molecular mechanismsexplaining the cardiac derangements induced by DOX were identified in past decades, thetranslation to clinical practice has remained elusive to date. This review examines the currentunderstanding of DOX-induced cardiomyopathy (DCM) with a focus on mitochondria, which wereincreasingly proven to be crucial determinants of DOX-induced cytotoxicity. We discuss DCMpathophysiology and epidemiology and DOX-induced detrimental effects on mitochondrialfunction, dynamics, biogenesis, and autophagy. Lastly, we review the current perspectives tocontrast the development of DCM, which is still a relatively diffused, invalidating, and life-threatening condition for cancer survivors.