Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Arterioscler Thromb Vasc Biol. 2021 Nov;41(11):2648-2660. doi: 10.1161/ATVBAHA.121.316697. Epub 2021 Sep 30.
Significant progress has been made in developing new treatments and refining the use of preexisting ones against cancer. Their successful use and the longer survival of cancer patients have been associated with reports of new cardiotoxicities and the better characterization of the previously known cardiac complications. Immunotherapies with monoclonal antibodies against specific cancer-promoting genes, chimeric antigen receptor T cells, and immune checkpoint inhibitors have been developed to fight cancer cells, but they can also show off-target effects on the heart. Some of these cardiotoxicities are thought to be due to nonspecific immune activation and inflammatory damage. Unlike immunotherapy-associated cardiotoxicities which are relatively new entities, there is extensive literature on anthracycline-induced cardiomyopathy. Here, we provide a brief overview of the cardiotoxicities of immunotherapies for the purpose of distinguishing them from anthracycline cardiomyopathy. This is especially relevant as the expansion of oncological treatments presents greater diagnostic challenges in determining the cause of cardiac dysfunction in cancer survivors with a history of multiple cancer treatments including anthracyclines and immunotherapies administered concurrently or serially over time. We then provide a focused review of the mechanisms proposed to underlie the development of anthracycline cardiomyopathy based on experimental data mostly in mouse models. Insights into its pathogenesis may stimulate the development of new strategies to identify patients who are susceptible to anthracycline cardiomyopathy while permitting low cardiac risk patients to receive optimal treatment for their cancer.
在开发新的癌症治疗方法和改进现有治疗方法方面已经取得了重大进展。癌症患者的成功治疗和更长的生存时间与新的心脏毒性的报告以及先前已知的心脏并发症的更好描述有关。已经开发出针对特定致癌基因的单克隆抗体、嵌合抗原受体 T 细胞和免疫检查点抑制剂等免疫疗法来对抗癌细胞,但它们也可能对心脏产生脱靶效应。这些心脏毒性中的一些被认为是由于非特异性免疫激活和炎症损伤引起的。与相对较新的免疫治疗相关的心脏毒性不同,蒽环类药物诱导性心肌病有大量的文献记载。在这里,我们简要概述了免疫疗法的心脏毒性,以便将其与蒽环类药物心肌病区分开来。这一点尤其重要,因为随着肿瘤治疗的扩展,对于同时或随着时间的推移接受多种癌症治疗(包括蒽环类药物和免疫疗法)的癌症幸存者,确定心脏功能障碍的原因带来了更大的诊断挑战。然后,我们根据主要在小鼠模型中获得的实验数据,重点回顾了蒽环类药物心肌病发展的潜在机制。对其发病机制的深入了解可能会刺激开发新策略,以识别易患蒽环类药物心肌病的患者,同时允许低心脏风险的患者接受癌症的最佳治疗。