Managing Doxorubicin Cardiotoxicity: Insights Into Molecular Mechanisms and Protective Strategies

Abstract

Cancer ranks as the second leading cause of death in the United States and poses a significant health challenge globally. Numerous therapeutic options exist for treating cancer, with chemotherapy being one of the most prominent. Chemotherapy involves the use of antineoplastic drugs, either alone or in combination with other medications, to target and kill cancer cells. However, these drugs can also adversely affect healthy cells, leading to various side effects. Among the most commonly used chemotherapy agents are anthracyclines, which include doxorubicin, daunorubicin, and epirubicin. Doxorubicin is particularly notable for its effectiveness but is also associated with significant cardiotoxicity, a common concern for patients undergoing chemotherapy. Unfortunately, there is currently no definitive treatment to prevent or reverse this cardiotoxicity. The cardiac effects of doxorubicin can manifest in several ways, including changes in electrocardiograms, arrhythmias, myocarditis, pericarditis, myocardial infarction, cardiomyopathy, heart failure, and congestive heart failure. These complications may arise during treatment, shortly after it concludes, or even weeks later. Various mechanisms have been proposed to explain doxorubicin-induced cardiotoxicity. Key factors include the inhibition of topoisomerase IIβ, mitochondrial damage, reactive oxygen species (ROS) production due to iron metabolism, increased oxidative stress, heightened inflammatory responses, and elevated rates of apoptosis and necrosis within cardiac tissue. This review article will provide a comprehensive overview of the current state of knowledge regarding doxorubicin-induced cardiomyopathy. We will explore the underlying molecular mechanisms contributing to this condition and discuss emerging therapeutic strategies aimed at mitigating its impact on cancer survivors.