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Intracellular Signaling Pathways Mediating Tyrosine Kinase Inhibitor Cardiotoxicity

Abstract

Tyrosine kinase inhibitors (TKIs) are used to treat several cancers; however, a myriad of adverse cardiotoxic effects remain a primary concern. Although hypertension (HTN) is the most common adverse effect reported with TKI therapy, incidents of arrhythmias (eg, QT prolongation, atrial fibrillation) and heart failure are also prevalent. These complications warrant further research toward understanding the mechanisms of TKI-induced cardiotoxicity. Recent literature has given some insight into the intracellular signaling pathways that may mediate TKI-induced cardiac dysfunction. In this article, we discuss the cardiotoxic effects of TKIs on cardiomyocyte function, signaling, and possible treatments.

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References
1.
Sternberg C, Davis I, Mardiak J, Szczylik C, Lee E, Wagstaff J . Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010; 28(6):1061-8. DOI: 10.1200/JCO.2009.23.9764. View

2.
Asnani A, Moslehi J, Adhikari B, Baik A, Beyer A, de Boer R . Preclinical Models of Cancer Therapy-Associated Cardiovascular Toxicity: A Scientific Statement From the American Heart Association. Circ Res. 2021; 129(1):e21-e34. PMC: 8423100. DOI: 10.1161/RES.0000000000000473. View

3.
Du Z, Lovly C . Mechanisms of receptor tyrosine kinase activation in cancer. Mol Cancer. 2018; 17(1):58. PMC: 5817791. DOI: 10.1186/s12943-018-0782-4. View

4.
del Peso L, Gonzalez-Garcia M, Page C, Herrera R, Nunez G . Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science. 1997; 278(5338):687-9. DOI: 10.1126/science.278.5338.687. View

5.
Abbaspour Babaei M, Kamalidehghan B, Saleem M, Huri H, Ahmadipour F . Receptor tyrosine kinase (c-Kit) inhibitors: a potential therapeutic target in cancer cells. Drug Des Devel Ther. 2016; 10:2443-59. PMC: 4975146. DOI: 10.2147/DDDT.S89114. View