Unveiling the Cardiotoxicity Conundrum: Navigating the Seas of Tyrosine Kinase Inhibitor Therapies

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of various solid and hematologic malignancies by targeting dysregulated signaling pathways critical for malignant cell growth. However, these therapeutic benefits are often accompanied by cardiotoxicities, such as hypertension, left ventricular dysfunction, QT prolongation, and tachyarrhythmias, among others. These cardiotoxicities post a significant challenge in clinical management, often limiting the use of otherwise effective therapies. The underlying mechanism of TKI-induced cardiotoxicity appears to be multifaceted, involving several pathways including: direct cardiomyocyte damage, mitochondrial dysfunction, endothelial damage, and disruption of signaling pathways critical for cardiac function. The range and severity of cardiotoxicities vary significantly across different TKIs, necessitating a comprehensive understanding of each agent’s specific cardiovascular risk profile. Preventing and managing TKI-induced cardiotoxicity requires a comprehensive, multidisciplinary approach. Early identification of at-risk patients through baseline cardiovascular risk assessments and appropriate monitoring during therapy is crucial. Strategies to mitigate cardiotoxic effects include dose modification, the use of cardioprotective agents, and temporary discontinuation of therapy. Additionally, decision making via multidisciplinary teams ensures minimization of cardiovascular complications while also continuing effective cancer treatment. Historically, data have been limited regarding cardiotoxicity and most cancer therapies, which certainly includes TKIs. This review aims to synthesize the current body of knowledge on TKI-associated cardiotoxicities, while highlighting the importance of vigilance and proactive management to minimize cardiovascular complications.