Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
Section of Cardiology, Department of Internal Medicine, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
Mol Cell Biochem. 2021 Aug;476(8):3099-3109. doi: 10.1007/s11010-021-04152-y. Epub 2021 Apr 9.
While anthracyclines (ACs) are a class of chemotherapeutic agents that have improved the prognosis of many women with breast cancer, it is one of the most cardiotoxic agents used to treat cancer. Despite their reported dose-dependent cardiotoxicity, AC-based chemotherapy has become the mainstay of breast cancer therapy due to its efficacy. Elucidating the mechanisms of anthracycline-mediated cardiotoxicity and associated therapeutic interventions continue to be the main focus in the field of cardio-oncology. Herein, we summarized the current literature surrounding the mechanisms of anthracycline-induced cardiotoxicity, including the role of topoisomerase II inhibition, generation of reactive oxygen species, and elevations in free radicals. Furthermore, this review highlights the molecular mechanisms of potential cardioprotective interventions in this setting. The benefits of pharmaceuticals, including dexrazoxane, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, statins, and antioxidants in this setting, are reviewed. Finally, the mechanisms of emerging preventative interventions within this patient population including nutraceuticals and aerobic exercise are explored.
虽然蒽环类药物（ACs）是一类化疗药物，已改善了许多乳腺癌女性的预后，但它也是用于治疗癌症的最具心脏毒性的药物之一。尽管据报道其具有剂量依赖性的心脏毒性，但由于其疗效，基于 AC 的化疗已成为乳腺癌治疗的主要方法。阐明蒽环类药物介导的心脏毒性的机制和相关的治疗干预措施仍然是心脏肿瘤学领域的主要重点。在此，我们总结了围绕蒽环类药物诱导的心脏毒性的机制的现有文献，包括拓扑异构酶 II 抑制、活性氧的产生和自由基的升高。此外，本综述强调了这种情况下潜在的心脏保护干预的分子机制。本文还回顾了在这种情况下，药物（包括右雷佐生、血管紧张素转换酶抑制剂、血管紧张素受体阻滞剂、β受体阻滞剂、他汀类药物和抗氧化剂）的益处。最后，探讨了包括营养保健品和有氧运动在内的该患者群体中新兴预防干预措施的机制。
