Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Turin, Italy; Department of Biology, College of Life Science and Technology, Jinan University, Guangzhou, China.
Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Turin, Italy; Department of Translational Medical Sciences, Federico II University, Naples, Italy.
Biochim Biophys Acta Mol Cell Res. 2020 Mar;1867(3):118493. doi: 10.1016/j.bbamcr.2019.06.007. Epub 2019 Jun 22.
Cardiotoxicity is a major drawback of anticancer therapies, often hindering optimal management of cancer. Among the most cardiotoxic agents are anthracyclines (AC) that, despite being cardiotoxic, are highly effective in the treatment of a wide variety of cancers, spanning from hematological malignancies to solid tumors. Modern imaging techniques can identify patients at risk of developing cardiotoxicity, but treatment options are still limited and ineffective, partly because the molecular mechanisms underlying AC cardiac side effects are still incompletely understood. Although AC cardiotoxicity was initially ascribed to the trigger of cell-damaging oxidative stress, antioxidants fail to prevent anthracycline-induced cardiotoxicity (AIC), suggesting the involvement of additional mechanisms. Among these, the cellular recycling process, named autophagy, recently emerged to play a key role in AIC, but whether autophagy activation is beneficial or detrimental in this context is still controversial. This review will summarize recent evidence on the role of autophagy in AIC in the attempt to reconcile the controversial findings in the field. Finally, we will describe major regulator of cardiac autophagy that may represent good candidates for therapeutic intervention in AIC.
心脏毒性是癌症治疗的一个主要缺点，常常阻碍癌症的最佳治疗。在最具心脏毒性的药物中，蒽环类药物（AC）虽然具有心脏毒性，但在治疗各种癌症方面非常有效，包括血液系统恶性肿瘤和实体瘤。现代成像技术可以识别出有发生心脏毒性风险的患者，但治疗选择仍然有限且无效，部分原因是蒽环类药物心脏副作用的分子机制仍不完全清楚。虽然 AC 心脏毒性最初归因于触发细胞损伤的氧化应激，但抗氧化剂不能预防蒽环类药物引起的心脏毒性（AIC），表明存在其他机制。在这些机制中，称为自噬的细胞再循环过程最近被发现在 AIC 中发挥关键作用，但在这种情况下自噬的激活是有益还是有害仍存在争议。这篇综述将总结自噬在 AIC 中的作用的最新证据，试图调和该领域有争议的发现。最后，我们将描述心脏自噬的主要调节剂，它们可能是 AIC 治疗干预的良好候选者。
