Off-Target Effects of Cancer Therapy on Development of Therapy-Induced Arrhythmia: A Review

BACKGROUND: Advances in cancer therapeutics have improved overall survival and prognosis in this patient population; however, this has come at the expense of cardiotoxicity including arrhythmia. SUMMARY: Cancer and its therapies are associated with cardiotoxicity via several mechanisms including inflammation, cardiomyopathy, and off-target effects. Among cancer therapies, anthracyclines and tyrosine kinase inhibitors (TKIs) are particularly known for their pro-arrhythmia effects. In addition to cardiomyopathy, anthracyclines may be pro-arrhythmogenic via reactive oxygen species (ROS) generation and altered calcium handling. TKIs may mediate their cardiotoxicity via inhibition of off-target tyrosine kinases. Ibrutinib-mediated inhibition of CSK may be responsible for the increased prevalence of atrial fibrillation. Further investigation is warranted to further elucidate the mechanisms behind arrhythmias in cancer therapies. KEY MESSAGES: Arrhythmias are a common cardiotoxicity of cancer therapies. Cancer therapies may induce arrhythmias via off-target effects. Understanding the mechanisms underlying arrhythmogenesis associated with cancer therapies may help design cancer therapies that can avoid these toxicities.