Cardiotoxicity Induced by Protein Kinase Inhibitors in Patients with Cancer

Abstract

Kinase inhibitors (KIs) represent a growing class of drugs directed at various protein kinases and used in the treatment of both solid tumors and hematologic malignancies. It is a heterogeneous group of compounds that are widely applied not only in different types of tumors but also in tumors that are positive for a specific predictive factor. This review summarizes common cardiotoxic effects of KIs, including hypertension, arrhythmias with bradycardia and QTc prolongation, and cardiomyopathy that can lead to heart failure, as well as less common effects such as fluid retention, ischemic heart disease, and elevated risk of thromboembolic events. The guidelines for cardiac monitoring and management of the most common cardiotoxic effects of protein KIs are discussed. Potential signaling pathways affected by KIs and likely contributing to cardiac damage are also described. Finally, the need for further research into the molecular mechanisms underlying the cardiovascular toxicity of these drugs is indicated.

Lazertinib: on the Way to Its Throne

“…Specifically, the risk of cardiac adverse events associated with osimertinib is a concern for clinicians. 42 43 The reported odds ratio for cardiac failure, atrial fibrillation, QT prolongation, myocardial infarction, and pericardial effusion when comparing osimertinib and other EGFR-TKIs were 2.2 (95% CI, 1.5–3.2), 2.1 (95% CI, 1.3–3.5), 6.6 (95% CI, 3.4–12.8), 1.2 (95% CI, 0.6–2.3), and 1.6 (95% CI, 0.8–3.3), respectively. 44 …”

Biomarkers of Trastuzumab-Induced Cardiac Toxicity in HER2- Positive Breast Cancer Patient Population

“…Numerous anticancer drugs are known to cause heart toxicity [ 10 ]. The risk of cardiovascular toxicity during the treatment of HER2-positive BC seems underestimated [ 11 ].…”

“…The data on cardiotoxicity incidence confirm the risk to be 3–26% for doxorubicin-based (type I cardiotoxicity) and 2–28% for trastuzumab treatment (TT) (type II)—trastuzumab-induced cardiotoxicity (TIC) [ 14 ]. Type I irreversible myocardial dysfunction is connected to myocardium destruction, while type II is related to the inhibition of physiological myocardial functioning, and is thought to be temporary [ 10 , 14 , 15 ]. However, numerous data show that TIC mechanisms are still evolving.…”

“…However, numerous data show that TIC mechanisms are still evolving. HER2-positive BC patients commonly receive both types of systemic treatment: chemotherapy and antiHER2 treatment thus enhanced cardiotoxicity induced by anthracyclines and trastuzumab-based regimens can be noted [ 10 , 14 , 15 ].…”

QTc prolongations as a result of drug interactions of CD4/6 inhibitors

“…Conclusion: protein kinase inhibitors used in molecularly-targeted oncology drugs are cardiotoxic and can cause various disorders of the cardiovascular system. This group of agents includes CDK 4/6 inhibitors that occasionally prolong the QTc interval [1]. Cyclin-dependent kinase 4/6 inhibitors are metabolized by CYP3A enzymes and inhibit CYP3A themselves.…”