Doxorubicin-Induced Cardiomyopathy in Children
Doxorubicin-Induced Cardiomyopathy in Children
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DOI：
10.1002/cphy.c180017
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发表时间：
2019-07-01
影响因子：
5.8
通讯作者：
Aune, Gregory J.
中科院分区：
文献类型：
--
作者：
Mancilla, Trevi R.;Iskra, Brian;Aune, Gregory J.
阿霉素引起的儿童癌症幸存者心脏毒性是一个日益严重的问题。随着各类儿童癌症的五年生存率继续提高，心血管疾病风险患者的人数正在稳步增加。阿霉素对发育中的心脏的影响不同于成人心脏，在一小部分接触阿霉素的患者中，儿童接触阿霉素会导致晚期不可逆的心肌病。值得注意的是，随着生存率的提高，迟发性毒性的发生率也在增加。到2020年，估计将有50万儿童癌症幸存者，其中超过5万人将遭受阿霉素引起的心脏毒性。迄今为止，大多数研究都集中在儿童癌症幸存者身上，主要通过精心设计的流行病学和回顾性队列研究来关注临床结果。临床前研究已经阐明了许多引起心肌细胞急性毒性的细胞机制。然而，需要在早发性和晚发性心脏毒性领域进行更多的研究，更重要的是需要提高对心脏环境中存在的其他细胞如何受到阿霉素暴露影响的科学理解。本综述的总体目标是简要总结阿霉素诱导心脏毒性的主要临床和临床前研究。由于受阿霉素暴露影响的患者的患病率继续增加，必须确定现有研究中的主要差距，并随后利用这些差距为未来几年制定适当的研究重点。设计良好的临床前研究模型将增强我们对阿霉素引起的心脏毒性的病理生理学的理解，并直接导致更好的诊断、治疗和预防。(c) 2019年美国生理学会。
Doxorubicin-induced cardiotoxicity in childhood cancer survivors is a growing problem. The population of patients at risk for cardiovascular disease is steadily increasing, as five-year survival rates for all types of childhood cancers continue to improve. Doxorubicin affects the developing heart differently from the adult heart and in a subset of exposed patients, childhood exposure leads to late, irreversible cardiomyopathy. Notably, the prevalence of late-onset toxicity is increasing in parallel with improved survival. By the year 2020, it is estimated that there will be 500,000 childhood cancer survivors and over 50,000 of them will suffer from doxorubicin-induced cardiotoxicity.The majority of the research to-date, concentrated on childhood cancer survivors, has focused mostly on clinical outcomes through well-designed epidemiological and retrospective cohort studies. Preclinical studies have elucidated many of the cellular mechanisms that elicit acute toxicity in cardiomyocytes. However, more research is needed in the areas of early- and late-onset cardiotoxicity and more importantly improving the scientific understanding of how other cells present in the cardiac milieu are impacted by doxorubicin exposure.The overall goal of this review is to succinctly summarize the major clinical and preclinical studies focused on doxorubicin-induced cardiotoxicity. As the prevalence of patients affected by doxorubicin exposure continues to increase, it is imperative that the major gaps in existing research are identified and subsequently utilized to develop appropriate research priorities for the coming years. Well-designed preclinical research models will enhance our understanding of the pathophysiology of doxorubicin-induced cardiotoxicity and directly lead to better diagnosis, treatment, and prevention. (c) 2019 American Physiological Society.