Anthracycline-induced cardiotoxicity: An overview from cellular structural perspective

Anthracyclines are broad-spectrum anticancer drugs, but their clinical use is limited due to their severe cardiotoxicity. Anthracycline-induced cardiotoxicity (AIC) remains a significant cause of heart disease-related mortality in many cancer survivors. The underlying mechanisms of AIC have been explored over the past few decades. Reactive oxygen species and drug-induced inhibition of topoisomerase II beta are well-studied mechanisms, with mitochondria being a prominently investigated organelle. Emerging mechanisms such as ferroptosis, Ca2+ overload, autophagy and inflammation mediators have been implicated in recent years. In this review, our goal is to summarize and update the roles of various mechanisms in AIC, focusing on different cellular levels and further explore promising therapeutic approaches targeting these organelles or pathways. [Display omitted] •Anthracyclines intercalate into DNA in the nucleus and inhibit Top2, leading to DNA DSB.•Anthracyclines disrupt ROS balance in mitochondria, causing oxidative stress and altering metabolic pathways to drive energy depletion.•Anthracyclines interfere with GPX4, IRP, TfR, and others, increasing free iron levels and leading to ferroptosis.•Anthracyclines enhance ubiquitination levels and disrupt lysosomal biogenesis, leading to interruption of autophagy.