This review highlights the central role of mitochondrial dysfunction in anthracycline-induced cardiotoxicity and suggests mitochondria-targeted drugs as potential therapeutic strategies.
Cardiac side effects are a major drawback of anticancer therapies, often requiring the use of low and less effective doses or even discontinuation of the drug. Among all the drugs known to cause severe cardiotoxicity are anthracyclines that, though being the oldest chemotherapeutic drugs, are still a mainstay in the treatment of solid and hematological tumors. The recent expansion of the field of Cardio-Oncology, a branch of cardiology dealing with prevention or treatment of heart complications due to cancer treatment, has greatly improved our knowledge of the molecular mechanisms behind anthracycline-induced cardiotoxicity (AIC). Despite excessive generation of reactive oxygen species was originally believed to be the main cause of AIC, recent evidence points to the involvement of a plethora of different mechanisms that, interestingly, mainly converge on deregulation of mitochondrial function. In this review, we will describe how anthracyclines affect cardiac mitochondria and how these organelles contribute to AIC. Furthermore, we will discuss how drugs specifically targeting mitochondrial dysfunction and/or mitochondria-targeted drugs could be therapeutically exploited to treat AIC.
Murabito et al. (Thu,) studied this question.