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.
Highlights
The incidence of cancer has been increasing worldwide
Protein Kinase inhibitors (KIs) can be classified into several families depending on the structure and ligand: epidermal growth factor receptor (EGFR) inhibitors; vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors; v-raf murine sarcoma viral oncogene homolog B (BRAF) 1/2 inhibitors; mitogen-activated protein kinase kinases 1 and 2 (MEK) inhibitors; anaplastic lymphoma kinase (ALK) inhibitors; Bruton tyrosine kinase (BTK) inhibitors; phosphoinositide 3-kinase (PI3K) inhibitors; cyclin-dependent kinase (CDK) 4/6 inhibitors; Janus kinases (JAK) inhibitors; BCR-ABL tyrosine kinase inhibitors; FMS-like tyrosine kinase-3 (FLT3) inhibitors; and stem cell factor receptor/platelet-derived growth factor receptor (KIT/PDGFRA) inhibitors (Figures 1 and 2)
Cardiomyopathy leading to heart failure is a serious adverse effect of treatment with various classes of KIs, including BCR-ABL kinase, c-KIT, BRAF/MEK, EGFR, and ALK inhibitors, as well as multitarget KIs used for metastatic RCC (mRCC) treatment
Summary
The incidence of cancer has been increasing worldwide. Data show that cancer may become the leading cause of death in some countries in the 21st century. The current options for systemic cancer treatment include chemotherapy, hormone therapy, targeted drugs, and immunotherapy, commonly used in combination. Protein kinase inhibitors (KIs) are a growing group of drugs used in the majority of cancer indications, including lung, breast, colorectal, kidney, liver, or thyroid cancer, and melanoma, soft tissue sarcoma, gastrointestinal stroma tumor (GIST), and various hematological malignancies [5,6] New strategies have changed the treatment paradigm in many types of cancer, which are considered to be chronic diseases rather than fatal diseases with a short life expectancy.
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