Intracellular Signaling Pathways Mediating Tyrosine Kinase Inhibitor Cardiotoxicity

Abstract

Tyrosine kinase inhibitors (TKIs) are used to treat several cancers; however, a myriad of adverse cardiotoxic effects remain a primary concern. Although hypertension (HTN) is the most common adverse effect reported with TKI therapy, incidents of arrhythmias (eg, QT prolongation, atrial fibrillation) and heart failure are also prevalent. These complications warrant further research toward understanding the mechanisms of TKI-induced cardiotoxicity. Recent literature has given some insight into the intracellular signaling pathways that may mediate TKI-induced cardiac dysfunction. In this article, we discuss the cardiotoxic effects of TKIs on cardiomyocyte function, signaling, and possible treatments.

Keywords: Arrhythmias; Cardio-oncology; Cardiotoxicity; Hypertension 5’ AMP-activated protein kinase (AMPK); Intracellular signaling; Phosphoinositide 3-kinase (PI3K) signaling; Tyrosine kinase inhibitors (TKIs); Vascular endothelial growth factor receptor (VEGFR).