Clinical Relevance and Mechanistic Underpinnings of Tyrosine Kinase Inhibitor Associated Cardiotoxicities

Tyrosine kinase inhibitors (TKIs) are a major backbone of cancer treatments across a range of malignancies. Observed adverse effects of these targeted therapies include a multitude of clinically relevant cardiotoxicities distinct from those of traditional cytotoxic chemotherapies. Over the past decade, TKI cardiotoxicities have gained growing recognition in the field of cardio-oncology. Here, we aim to review clinically relevant cardiotoxicities of TKIs and incorporate relevant preclinical mechanistic data.

Each TKI class and generation within each class have been associated with a unique cardiotoxicity profile. Broadly, documented cardiotoxicities include arrythmia (atrial and ventricular), heart failure, and vascular complications (thrombosis, endothelial dysfunction, hypertension, and atherosclerosis). Recent and progressing basic investigations have begun to unveil mechanistic underpinnings of these toxicities, such as identifying off-target perturbations of specific signaling pathways, but much more work is needed.

Here, we provide a review of the most clinically relevant cardiovascular toxicities to raise awareness when caring for patients on these drugs. TKIs exemplify the complexity in systemic manipulation of fundamental molecular pathways effects. Translational research in cardio-oncology is of paramount importance which can offer not only a way to better monitor (and prevent) known toxicities, but to more broadly understand and define novel molecular pathways relevant to cardiovascular disease.