Cardiotoxicity of antiangiogenic drugs: causes and mechanisms

Therapy with angiogenesis inhibitors is undoubtedly an advancement in cancer treatment; however, it is associated with a risk of developing cardiotoxicity, which most often manifests in myocardial contractile dysfunction or an increased risk of thromboembolic events. Heart failure is observed in 2–4% of patients treated with bevacizumab and in 3–8% of patients on antiangiogenic tyrosine kinase inhibitors. The proposed pathomechanisms underlying the impairment in systolic function during antiangiogenic drug treatment include mitochondrial dysfunction, a secondary reduction in cardiomyocyte ATP production and redox imbalance, which may contribute to pathological states known as “free radical diseases”. Additionally, therapy with angiogenesis inhibitors may also cause cardiac oxidative stress. The risk factors for cardiac complications include arterial hypertension, which is a known “class effect” of this class of drugs, as well as a number of other factors such as age, comorbidities, prior radiotherapy and baseline left ventricular ejection fraction. The cardiovascular diseases are still the first cause of death in the world. The more effective oncological treatment becomes, the more often comorbidities occur. This fact seems to demand interdisciplinary approach from investigators and practitioners. This article presents the current state of knowledge on the molecular mechanisms of cardiotoxicity of antiangiogenic drugs used in routine clinical practice.