Cancer therapy-induced cardiotoxicity: mechanisms and mitigations

Figures

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  Fig. 1. Cancer therapies and cancer therapy-related cardiovascular toxicity. Anthracyclines induce cardiotoxicity via increased ROS production, topoisomerase II poisoning, and mitochondrial disruption. Monoclonal antibodies disrupts NRG-1/ERBB2 signalling, inducing oxidative stress and apoptotic pathways, especially when combined with anthracyclines. TKIs impair endothelial NO synthase activity, causing endothelial dysfunction, and vasoconstriction, while also promoting mitochondrial dysfunction in cardiomyocytes. ICIs induce myocarditis through T-cell infiltration and cytokine-mediated inflammation. (Tyrosine kinase inhibitors- TKIs, immune checkpoint inhibitors- ICIs, nitric oxide- NO, electron transport chain- ETC, reactive oxygen species- ROS)

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  Fig. 2. The diagram illustrates the mechanisms of radiation-induced cardiac toxicity. Radiation-induced cardiomyocyte damage occurs due to oxidative stress, and DNA damage. Oxidative stress triggers pro-inflammatory cytokines, pro-apoptotic gene activation, increased malondialdehyde and xanthine oxidase, and cyclooxygenase-2 activation, resulting in microvascular injury, cell death, myocardial stiffening, and reduced left ventricular filling. In endothelial cells, oxidative stress promotes senescence, SASP activation, and immune cell recruitment, contributing to fibrosis through fibroblast activation, fatty streak formation, and atherosclerosis progression. These processes result in microvascular damage, diastolic dysfunction, arrhythmias, cardiomyopathy, and CAD, highlighting the interconnected pathways in radiation-induced cardiac toxicity. (reactive oxygen species- ROS, senescence-associated secretory phenotype- SASP, coronary artery disease (CAD)

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  Fig. 3. Strategies to mitigate cardiotoxicity in cancer treatments