New signal transduction paradigms in anthracycline-induced cardiotoxicity
New signal transduction paradigms in anthracycline-induced cardiotoxicity
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DOI：
10.1016/j.bbamcr.2016.01.021
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发表时间：
2016-07-01
影响因子：
5.1
通讯作者：
Hirsch, Emilio
中科院分区：
文献类型：
--
作者：
Ghigo, Alessandra;Li, Mingchuan;Hirsch, Emilio
蒽环类，如阿霉素，是治疗多种人类癌症，包括实体瘤和血液恶性肿瘤的最有效和广泛使用的化疗剂。然而，它们的临床使用受到严重的心脏毒性副作用的阻碍，并且癌症治疗相关的心脏病已成为癌症幸存者发病率和死亡率的主要原因。因此，确定限制蒽环类抗生素心脏毒性同时保留抗肿瘤功效的治疗策略代表了心脏肿瘤学家当前面临的挑战。蒽环类药物的心脏毒性最初归因于该类药物破坏铁代谢并产生过量活性氧（ROS）的能力。然而，铁螯合剂和抗氧化剂的小型临床试验未能提供任何益处，并表明多柔比星心脏毒性不仅仅是由于氧化还原循环。新出现的解释包括蒽环类药物依赖性调节控制DNA损伤反应、心肌细胞存活、心脏炎症、能量应激和基因表达调节的主要信号通路。本文将总结最近的研究，揭开复杂的网络机制的阿霉素介导的心脏毒性，并确定新的药物球员预防心脏病的癌症患者。这篇文章是由Marcus Schaub和Hughes Abriel编辑的题为：心肌细胞生物学：心脏中发育和环境线索的整合的特刊的一部分。(c)© 2016 Elsevier B.V.版权所有。
Anthracyclines, such as doxorubicin, are the most potent and widely used chemotherapeutic agents for the treatment of a variety of human cancers, including solid tumors and hematological malignancies. However, their clinical use is hampered by severe cardiotoxic side effects and cancer therapy-related heart disease has become a leading cause of morbidity and mortality among cancer survivors. The identification of therapeutic strategies limiting anthracycline cardiotoxicity with preserved antitumor efficacy thus represents the current challenge of cardiooncologists. Anthracycline cardiotoxicity has been originally ascribed to the ability of this class of drugs to disrupt iron metabolism and generate excess of reactive oxygen species (ROS). However, small clinical trials with iron chelators and anti-oxidants failed to provide any benefit and suggested that doxorubicin cardiotoxicity is not solely due to redox cycling. New emerging explanations include anthracycline-dependent regulation of major signaling pathways controlling DNA damage response, cardiomyocyte survival, cardiac inflammation, energetic stress and gene expression modulation. This review will summarize recent studies unraveling the complex web of mechanisms of doxorubicin-mediated cardiotoxicity, and identifying new druggable players for the prevention of heart disease in cancer patients. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. (c) 2016 Elsevier B.V. All rights reserved.