Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
The Institute for Stem Cell Biology and Regenerative Medicine, 265 Campus Drive, 3rd Floor, Stanford, CA, USA.
Eur Heart J. 2019 Jun 7;40(22):1764-1770. doi: 10.1093/eurheartj/ehx811.
Cardiotoxic effects from cancer therapy are a major cause of morbidity during cancer treatment. Unexpected toxicity can occur during treatment and/or after completion of therapy, into the time of cancer survivorship. While older drugs such as anthracyclines have well-known cardiotoxic effects, newer drugs such as tyrosine kinase inhibitors, proteasome inhibitors, and immunotherapies also can cause diverse cardiovascular and metabolic complications. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are increasingly being used as instruments for disease modelling, drug discovery, and mechanistic toxicity studies. Promising results with hiPSC-CM chemotherapy studies are raising hopes for improving cancer therapies through personalized medicine and safer drug development. Here, we review the cardiotoxicity profiles of common chemotherapeutic agents as well as efforts to model them in vitro using hiPSC-CMs.
癌症治疗的心脏毒性是癌症治疗期间发病的主要原因。在治疗期间和/或治疗完成后，甚至在癌症生存期间，都可能会出现意外的毒性。虽然像蒽环类药物这样的老药具有众所周知的心脏毒性，但像酪氨酸激酶抑制剂、蛋白酶体抑制剂和免疫疗法等新药也会引起不同的心血管和代谢并发症。人类诱导多能干细胞衍生的心肌细胞（hiPSC-CMs）越来越多地被用作疾病建模、药物发现和机制毒性研究的工具。hiPSC-CM 化疗研究的有希望结果，使人们对通过个性化医学和更安全的药物开发来改善癌症治疗产生了希望。在这里，我们综述了常见化疗药物的心脏毒性特征，以及使用 hiPSC-CMs 进行体外模型构建的努力。
