Cancer therapy-induced cardiotoxicity: mechanisms and mitigations

Abstract Cancer treatments like chemotherapy, radiotherapy, and combined immunotherapies have significantly increased patient survival. However, these treatments are frequently linked to cardiovascular toxicity, which has a significant impact on clinical outcomes and patient well-being. Chemotherapy, targeted therapy, and radiotherapy induce significant cellular stress in cardiomyocytes and endothelial cells, causing DNA damage, activating pro-inflammatory and pro-apoptotic signalling pathways. Cumulative damage causes cardiomyocyte loss, followed by fibrosis, resulting in pathological structural and functional remodelling of the myocardium. Endothelial cell damage disrupts vascular integrity, increasing the risk of atherosclerosis, coronary artery disease, and ischaemia. Over time, these changes can lead to clinical conditions like dilated and restrictive cardiomyopathy, which are frequently accompanied by arrhythmias and can result in heart failure and sudden cardiac death. To overcome this problem, the novel field of cardio-oncology aims to provide effective cancer treatments with a multifaceted cardioprotection approach involving pharmacological, diagnostic, natural compounds, and lifestyle interventions during and after cancer therapy. In this review, we cover the important cancer therapies, and their cardiotoxic mechanisms and detail different cardioprotective strategies aimed at mitigating these adverse effects and improve patient outcomes.