Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
Cells. 2021 Oct 21;10(11):2823. doi: 10.3390/cells10112823.
The therapeutic landscape for the treatment of cancer has evolved significantly in recent decades, aided by the development of effective oncology drugs. However, many cancer drugs are often poorly tolerated by the body and in particular the cardiovascular system, causing adverse and sometimes fatal side effects that negate the chemotherapeutic benefits. The prevalence and severity of chemotherapy-induced cardiotoxicity warrants a deeper investigation of the mechanisms and implicating factors in this phenomenon, and a consolidation of scientific efforts to develop mitigating strategies. Aiding these efforts is the emergence of induced pluripotent stem cells (iPSCs) in recent years, which has allowed for the generation of iPSC-derived cardiomyocytes (iPSC-CMs): a human-based, patient-derived, and genetically variable platform that can be applied to the study of chemotherapy-induced cardiotoxicity and beyond. After surveying chemotherapy-induced cardiotoxicity and the associated chemotherapeutic agents, we discuss the use of iPSC-CMs in cardiotoxicity modeling, drug screening, and other potential applications. Improvements to the iPSC-CM platform, such as the development of more adult-like cardiomyocytes and ongoing advances in biotechnology, will only enhance the utility of iPSC-CMs in both basic science and clinical applications.
近年来，随着有效的肿瘤药物的发展，癌症治疗的治疗景观发生了重大变化。然而，许多癌症药物通常在体内，特别是心血管系统中耐受性差，导致不良且有时致命的副作用，从而抵消了化疗的益处。化疗引起的心脏毒性的流行率和严重程度需要更深入地研究这种现象的机制和牵连因素，并整合科学努力来开发缓解策略。近年来诱导多能干细胞（iPSCs）的出现为此提供了帮助，它允许生成 iPSC 衍生的心肌细胞（iPSC-CMs）：这是一种基于人类的、源自患者的、遗传可变的平台，可用于研究化疗引起的心脏毒性及其它方面。在调查了化疗引起的心脏毒性和相关的化疗药物后，我们讨论了 iPSC-CMs 在心脏毒性建模、药物筛选和其他潜在应用中的使用。iPSC-CM 平台的改进，例如开发更像成人的心肌细胞和生物技术的持续进步，将只会增强 iPSC-CMs 在基础科学和临床应用中的实用性。
