Molecular Mechanisms of Cardiovascular Toxicity of Targeted Cancer Therapeutics
Molecular Mechanisms of Cardiovascular Toxicity of Targeted Cancer Therapeutics
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DOI：
10.1161/circresaha.109.206920
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发表时间：
2010-01-08
影响因子：
20.1
通讯作者：
Force, Thomas
中科院分区：
文献类型：
--
作者：
Cheng, Hui;Force, Thomas
在2002年，Hoshijima和Chien在很大程度上在驱动癌症的信号传导途径的失调与驱动心脏肥大的信号传导途径的失调之间进行了理论上的比较（Hoshijima M，Chien KR.《临床投资杂志》2002;109：849-855）。从表面上看，这种说法似乎延伸了理性的界限，因为癌细胞以其增殖能力而闻名，而成年心肌细胞，除非在特殊情况下，终末分化，不能重新进入细胞周期。然而，在更仔细的研究中，在驱动肿瘤发生的信号通路和调节心肌细胞肥大反应和存活的信号通路之间存在许多相似之处。事实上，这个问题似乎是心脏毒性的核心（通常表现为扩张型心肌病），这可能是由通常称为“靶向治疗”的药物治疗引起的，这些药物靶向癌症中失调的特定蛋白激酶。在此，我们研究了靶向治疗的心脏毒性，重点是潜在的分子机制，从而允许理解问题，但也允许识别新的，有时令人惊讶的，由蛋白激酶在心脏中发挥的作用。(Circ Res. 2010;106：21-34.）
In 2002, Hoshijima and Chien drew largely theoretical parallels between the dysregulation of the signaling pathways driving cancer and those driving cardiac hypertrophy (Hoshijima M, Chien KR. J Clin Invest. 2002;109:849-855). On the surface, this statement appeared to stretch the limits of reason, given the fact that cancer cells are known for their proliferative capacity, and adult cardiomyocytes are, except under unusual circumstances, terminally differentiated and incapable of re-entering the cell cycle. However, on closer examination, there are numerous parallels between signaling pathways that drive tumorigenesis and signaling pathways that regulate hypertrophic responses and survival in cardiomyocytes. Indeed, this issue appears to be at the core of the cardiotoxicity (often manifest as a dilated cardiomyopathy) that can result from treatment with agents typically referred to as "targeted therapeutics," which target specific protein kinases that are dysregulated in cancer. Herein, we examine the cardiotoxicity of targeted therapeutics, focusing on the underlying molecular mechanisms, thereby allowing an understanding of the problem but also allowing the identification of novel, and sometimes surprising, roles played by protein kinases in the heart. (Circ Res. 2010;106:21-34.)