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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: Cheng, Mengfei, Yang, Fang, Liu, Jiahui, Yang, Dan, Zhang, Shuo, Yu, Yang, Jiang, Shuai, Dong, Mei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639698/
https://www.ncbi.nlm.nih.gov/pubmed/34869670
http://dx.doi.org/10.3389/fcvm.2021.758010
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author Cheng, Mengfei
Yang, Fang
Liu, Jiahui
Yang, Dan
Zhang, Shuo
Yu, Yang
Jiang, Shuai
Dong, Mei
author_facet Cheng, Mengfei
Yang, Fang
Liu, Jiahui
Yang, Dan
Zhang, Shuo
Yu, Yang
Jiang, Shuai
Dong, Mei
author_sort Cheng, Mengfei
collection PubMed
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.
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spelling pubmed-86396982021-12-04 Tyrosine Kinase Inhibitors-Induced Arrhythmias: From Molecular Mechanisms, Pharmacokinetics to Therapeutic Strategies Cheng, Mengfei Yang, Fang Liu, Jiahui Yang, Dan Zhang, Shuo Yu, Yang Jiang, Shuai Dong, Mei Front Cardiovasc Med Cardiovascular Medicine 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. Frontiers Media S.A. 2021-11-19 /pmc/articles/PMC8639698/ /pubmed/34869670 http://dx.doi.org/10.3389/fcvm.2021.758010 Text en Copyright © 2021 Cheng, Yang, Liu, Yang, Zhang, Yu, Jiang and Dong. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Cheng, Mengfei
Yang, Fang
Liu, Jiahui
Yang, Dan
Zhang, Shuo
Yu, Yang
Jiang, Shuai
Dong, Mei
Tyrosine Kinase Inhibitors-Induced Arrhythmias: From Molecular Mechanisms, Pharmacokinetics to Therapeutic Strategies
title 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_short 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
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639698/
https://www.ncbi.nlm.nih.gov/pubmed/34869670
http://dx.doi.org/10.3389/fcvm.2021.758010
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