Use of hiPSC to explicate genomic predisposition to anthracycline-induced cardiotoxicity.
Use of hiPSC to explicate genomic predisposition to anthracycline-induced cardiotoxicity.
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DOI：
10.2217/pgs-2020-0104
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发表时间：
2021-01
期刊：
影响因子：
2.1
通讯作者：
Tarek Magdy;P. Burridge
中科院分区：
文献类型：
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作者：
Tarek Magdy;P. Burridge
蒽环类药物家族的抗癌药物通常与可能对心脏造成严重毒性有关。为了解决为什么特定患者易患蒽环类药物诱导的心脏毒性（AIC）的问题，研究人员进行了大量的药物基因组学研究，并确定了60多个与AIC相关的基因座。迄今为止，这些已确定的基因座尚未发展成为美国fda批准的生物标志物，用于常规临床实践。随着人类诱导的多能干细胞衍生心肌细胞的应用、测序技术和基因组编辑技术的进步，与AIC相关的变异现在可以在人体模型中得到验证。在这里，我们从人类诱导的多能干细胞衍生的心肌细胞如何用于帮助更好地解释AIC的基因组偏好的角度，提供了与AIC相关的已知遗传变异的全面概述。
The anticancer agents of the anthracycline family are commonly associated with the potential to cause severe toxicity to the heart. To solve the question of why particular a patient is predisposed to anthracycline-induced cardiotoxicity (AIC), researchers have conducted numerous pharmacogenomic studies and identified more than 60 loci associated with AIC. To date, none of these identified loci have been developed into US FDA-approved biomarkers for use in routine clinical practice. With advances in the application of human-induced pluripotent stem cell-derived cardiomyocytes, sequencing technologies and genomic editing techniques, variants associated with AIC can now be validated in a human model. Here, we provide a comprehensive overview of known genetic variants associated with AIC from the perspective of how human-induced pluripotent stem cell-derived cardiomyocytes can be used to help better explain the genomic predilection to AIC.