Toronto General Hospital Research Institute, 101 College St., Toronto, Canada.
Peter Munk Cardiac Centre, University Health Network, 200 Elizabeth St., Toronto, Canada.
Clin Sci (Lond). 2020 Jul 17;134(13):1859-1885. doi: 10.1042/CS20190653.
Despite the known risk of cardiotoxicity, anthracyclines are widely prescribed chemotherapeutic agents. They are broadly characterized as being a robust effector of cellular apoptosis in rapidly proliferating cells through its actions in the nucleus and formation of reactive oxygen species (ROS). And, despite the early use of dexrazoxane, no effective treatment strategy has emerged to prevent the development of cardiomyopathy, despite decades of study, suggesting that much more insight into the underlying mechanism of the development of cardiomyopathy is needed. In this review, we detail the specific intracellular activities of anthracyclines, from the cell membrane to the sarcoplasmic reticulum, and highlight potential therapeutic windows that represent the forefront of research into the underlying causes of anthracycline-induced cardiomyopathy.
尽管已知具有心脏毒性风险，但蒽环类抗生素仍被广泛开为化疗药物。它们通过在细胞核中的作用和活性氧（ROS）的形成，广泛被认为是快速增殖细胞中细胞凋亡的有效诱导剂。尽管早期使用了右雷佐生，但尽管经过了几十年的研究，仍未出现有效的治疗策略来预防心肌病的发生，这表明我们需要更深入地了解心肌病发展的潜在机制。在这篇综述中，我们详细介绍了蒽环类抗生素从细胞膜到肌浆网的具体细胞内活性，并强调了潜在的治疗窗口，这些窗口代表了蒽环类抗生素诱导的心肌病潜在原因研究的前沿。
