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 mechanisms explaining the cardiac derangements induced by DOX were identified in past decades, the translation to clinical practice has remained elusive to date. This review examines the current understanding of DOX-induced cardiomyopathy (DCM) with a focus on mitochondria, which were increasingly proven to be crucial determinants of DOX-induced cytotoxicity. We discuss DCM pathophysiology and epidemiology and DOX-induced detrimental effects on mitochondrial function, dynamics, biogenesis, and autophagy. Lastly, we review the current perspectives to contrast the development of DCM, which is still a relatively diffused, invalidating, and life-threatening condition for cancer survivors.

Automated summary

Cardiotoxicity is a major side effect of doxorubicin treatment, affecting nearly 30% of patients within 5 years after chemotherapy. Despite identifying various molecular mechanisms explaining the cardiac derangements induced by doxorubicin, the translation to clinical practice remains challenging. This review focuses on mitochondria and discusses the pathophysiology, epidemiology, and detrimental effects of doxorubicin on mitochondrial function.