Tyrosine Kinase Inhibitors-Induced Arrhythmias: From Molecular Mechanisms, Pharmacokinetics to Therapeutic Strategies

With the development of anti-tumor drugs, tyrosine kinase inhibitors (TKIs) are an indispensable part of targeted therapy. They can be superior to traditional chemotherapeutic drugs in selectivity, safety, and efficacy. However, they have been found to be associated with serious adverse effects in u...

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Autores principales:	Mengfei Cheng, Fang Yang, Jiahui Liu, Dan Yang, Shuo Zhang, Yang Yu, Shuai Jiang, Mei Dong
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	TKIs QT prolongation atrial fibrillation molecule mechanism therapeutic strategies pharmacokinetics Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/55ad76f9d3e0435eaee247780c1c1fba
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id	oai:doaj.org-article:55ad76f9d3e0435eaee247780c1c1fba
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spelling	oai:doaj.org-article:55ad76f9d3e0435eaee247780c1c1fba2021-11-19T05:22:02ZTyrosine Kinase Inhibitors-Induced Arrhythmias: From Molecular Mechanisms, Pharmacokinetics to Therapeutic Strategies2297-055X10.3389/fcvm.2021.758010https://doaj.org/article/55ad76f9d3e0435eaee247780c1c1fba2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.758010/fullhttps://doaj.org/toc/2297-055XWith the development of anti-tumor drugs, tyrosine kinase inhibitors (TKIs) are an indispensable part of targeted therapy. They can be superior to traditional chemotherapeutic drugs in selectivity, safety, and efficacy. However, they have been found to be associated with serious adverse effects in use, such as myocardial infarction, fluid retention, hypertension, and rash. Although TKIs induced arrhythmia with a lower incidence than other cardiovascular diseases, much clinical evidence indicated that adequate attention and management should be provided to patients. This review focuses on QT interval prolongation and atrial fibrillation (AF) which are conveniently monitored in clinical practice. We collected data about TKIs, and analyzed the molecule mechanism, discussed the actual clinical evidence and drug-drug interaction, and provided countermeasures to QT interval prolongation and AF. We also pooled data to show that both QT prolongation and AF are related to their multi-target effects. Furthermore, more than 30 TKIs were approved by the FDA, but most of the novel drugs had a small sample size in the preclinical trial and risk/benefit assessments were not perfect, which led to a suspension after listing, like nilotinib. Similarly, vandetanib exhibits the most significant QT prolongation and ibrutinib exhibits the highest incidence in AF, but does not receive enough attention during treatment.Mengfei ChengFang YangJiahui LiuDan YangShuo ZhangYang YuShuai JiangMei DongFrontiers Media S.A.articleTKIsQT prolongationatrial fibrillationmolecule mechanismtherapeutic strategiespharmacokineticsDiseases of the circulatory (Cardiovascular) systemRC666-701ENFrontiers in Cardiovascular Medicine, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	TKIs QT prolongation atrial fibrillation molecule mechanism therapeutic strategies pharmacokinetics Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	TKIs QT prolongation atrial fibrillation molecule mechanism therapeutic strategies pharmacokinetics Diseases of the circulatory (Cardiovascular) system RC666-701 Mengfei Cheng Fang Yang Jiahui Liu Dan Yang Shuo Zhang Yang Yu Shuai Jiang Mei Dong Tyrosine Kinase Inhibitors-Induced Arrhythmias: From Molecular Mechanisms, Pharmacokinetics to Therapeutic Strategies
description	With the development of anti-tumor drugs, tyrosine kinase inhibitors (TKIs) are an indispensable part of targeted therapy. They can be superior to traditional chemotherapeutic drugs in selectivity, safety, and efficacy. However, they have been found to be associated with serious adverse effects in use, such as myocardial infarction, fluid retention, hypertension, and rash. Although TKIs induced arrhythmia with a lower incidence than other cardiovascular diseases, much clinical evidence indicated that adequate attention and management should be provided to patients. This review focuses on QT interval prolongation and atrial fibrillation (AF) which are conveniently monitored in clinical practice. We collected data about TKIs, and analyzed the molecule mechanism, discussed the actual clinical evidence and drug-drug interaction, and provided countermeasures to QT interval prolongation and AF. We also pooled data to show that both QT prolongation and AF are related to their multi-target effects. Furthermore, more than 30 TKIs were approved by the FDA, but most of the novel drugs had a small sample size in the preclinical trial and risk/benefit assessments were not perfect, which led to a suspension after listing, like nilotinib. Similarly, vandetanib exhibits the most significant QT prolongation and ibrutinib exhibits the highest incidence in AF, but does not receive enough attention during treatment.
format	article
author	Mengfei Cheng Fang Yang Jiahui Liu Dan Yang Shuo Zhang Yang Yu Shuai Jiang Mei Dong
author_facet	Mengfei Cheng Fang Yang Jiahui Liu Dan Yang Shuo Zhang Yang Yu Shuai Jiang Mei Dong
author_sort	Mengfei Cheng
title	Tyrosine Kinase Inhibitors-Induced Arrhythmias: From Molecular Mechanisms, Pharmacokinetics to Therapeutic Strategies
title_short	Tyrosine Kinase Inhibitors-Induced Arrhythmias: From Molecular Mechanisms, Pharmacokinetics to Therapeutic Strategies
title_full	Tyrosine Kinase Inhibitors-Induced Arrhythmias: From Molecular Mechanisms, Pharmacokinetics to Therapeutic Strategies
title_fullStr	Tyrosine Kinase Inhibitors-Induced Arrhythmias: From Molecular Mechanisms, Pharmacokinetics to Therapeutic Strategies
title_full_unstemmed	Tyrosine Kinase Inhibitors-Induced Arrhythmias: From Molecular Mechanisms, Pharmacokinetics to Therapeutic Strategies
title_sort	tyrosine kinase inhibitors-induced arrhythmias: from molecular mechanisms, pharmacokinetics to therapeutic strategies
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/55ad76f9d3e0435eaee247780c1c1fba
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Tyrosine Kinase Inhibitors-Induced Arrhythmias: From Molecular Mechanisms, Pharmacokinetics to Therapeutic Strategies

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