Arrhythmogenic effects of tyrosine kinase inhibitors: A narrative review

SummaryTyrosine kinase inhibitors (TKIs) are essential in cancer therapy but increasingly linked to arrhythmias, including long QT syndrome (LQT), atrial fibrillation, and ventricular arrhythmias. This review synthesizes current evidence on the arrhythmogenic potential of TKIs across drug classes and targets. Literature was sourced from PubMed, Google Scholar, and regulatory data up to November 2024. TKIs such as endothelial growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), FLT3, breakpoint cluster region-Abelson murine leukemia viral oncogene homolog (BCR-ABL), vascular endothelial growth factor receptor (VEGFR), and Bruton's tyrosine kinase (BTK) inhibitors are associated with diverse arrhythmias. Mechanisms include ion channel inhibition (IKr, INa, ICa, L), disrupted calcium handling via SERCA2a and phospholamban, and suppression of PI3K/Akt signaling. Inflammatory pathways, notably S100A8/A9-TLR4-NLRP3 activation, further contribute to proarrhythmic effects. These findings emphasize the need for individualized risk assessment, close monitoring, and mechanistically informed clinical management to minimize cardiac toxicity.