蒽环类药物引起心脏毒性的分子机制的更新。
An update of the molecular mechanisms underlying anthracycline induced cardiotoxicity.
发表日期:2024
作者:
Sicong Xie, Yuwei Sun, Xuan Zhao, Yiqun Xiao, Fei Zhou, Liang Lin, Wei Wang, Bin Lin, Zun Wang, Zixuan Fang, Lei Wang, Yang Zhang
来源:
Frontiers in Pharmacology
摘要:
蒽环类药物主要有阿霉素、表柔比星、吡柔比星、阿克拉霉素等,广泛用于治疗多种恶性肿瘤,如乳腺癌、消化道肿瘤、淋巴瘤等。随着蒽环类药物在体内的蓄积,可诱发严重的心脏损害,限制了其临床应用。蒽环类药物引起心脏毒性的机制尚不清楚。本综述概述了蒽环类药物引起的不同类型的心脏损伤,并深入研究了这些损伤背后的分子机制。心脏损伤主要涉及心肌细胞功能的改变和病理性细胞死亡,包括线粒体功能障碍、拓扑异构酶抑制、铁离子代谢破坏、肌原纤维降解和氧化应激。重点介绍了蒽环类药物心脏毒性的摄取和转运机制,以及iPSC在心脏毒性研究中的作用和突破。更新了选定的新型心脏保护疗法和机制。研究了动物实验中与蒽环类药物心脏毒性相关的机制和保护策略,并讨论了人类和动物模型中药物损伤的定义。了解这些分子机制对于减轻蒽环类药物引起的心脏毒性和指导开发更安全的癌症治疗方法至关重要。版权所有 © 2024 Xie, Sun, Zhao, Shaw, Zhou, Lin, Wang, Lin, Wang, Fang, Wang和张。
Anthracycline drugs mainly include doxorubicin, epirubicin, pirarubicin, and aclamycin, which are widely used to treat a variety of malignant tumors, such as breast cancer, gastrointestinal tumors, lymphoma, etc. With the accumulation of anthracycline drugs in the body, they can induce serious heart damage, limiting their clinical application. The mechanism by which anthracycline drugs cause cardiotoxicity is not yet clear. This review provides an overview of the different types of cardiac damage induced by anthracycline-class drugs and delves into the molecular mechanisms behind these injuries. Cardiac damage primarily involves alterations in myocardial cell function and pathological cell death, encompassing mitochondrial dysfunction, topoisomerase inhibition, disruptions in iron ion metabolism, myofibril degradation, and oxidative stress. Mechanisms of uptake and transport in anthracycline-induced cardiotoxicity are emphasized, as well as the role and breakthroughs of iPSC in cardiotoxicity studies. Selected novel cardioprotective therapies and mechanisms are updated. Mechanisms and protective strategies associated with anthracycline cardiotoxicity in animal experiments are examined, and the definition of drug damage in humans and animal models is discussed. Understanding these molecular mechanisms is of paramount importance in mitigating anthracycline-induced cardiac toxicity and guiding the development of safer approaches in cancer treatment.Copyright © 2024 Xie, Sun, Zhao, Xiao, Zhou, Lin, Wang, Lin, Wang, Fang, Wang and Zhang.