Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
Antioxid Redox Signal. 2020 May 20;32(15):1098-1114. doi: 10.1089/ars.2020.8019. Epub 2020 Mar 5.
The cardiac side effects of hematological treatments are a major issue of the growing population of cancer survivors, often affecting patient survival even more than the tumor for which the treatment was initially prescribed. Among the most cardiotoxic drugs are anthracyclines (ANTs), highly potent antitumor agents, which still represent a mainstay in the treatment of hematological and solid tumors. Unfortunately, diagnosis, prevention, and treatment of cardiotoxicity are still unmet clinical needs, which call for a better understanding of the molecular mechanism behind the pathology. This review article will discuss recent findings on the pathomechanisms underlying the cardiotoxicity of ANTs, spanning from DNA and mitochondrial damage to calcium homeostasis, autophagy, and apoptosis. Special emphasis will be given to the role of reactive oxygen species and their interplay with major signaling pathways. Although new promising therapeutic targets and new drugs have started to be identified, their efficacy has been mainly proven in preclinical studies and requires clinical validation. Future studies are awaited to confirm the relevance of recently uncovered targets, as well as to identify new druggable pathways, in more clinically relevant models, including, for example, human induced pluripotent stem cell-derived cardiomyocytes.
血液系统治疗的心脏副作用是癌症幸存者这一不断增长人群的主要问题，其对患者生存的影响常常甚于最初治疗所针对的肿瘤。在最具心脏毒性的药物中，蒽环类药物（ANTs）是一种高效抗肿瘤药物，在血液系统肿瘤和实体瘤的治疗中仍占有重要地位。不幸的是，心脏毒性的诊断、预防和治疗仍然是尚未满足的临床需求，这需要我们更好地了解其发病机制背后的分子机制。 这篇综述文章将讨论 ANTs 心脏毒性的发病机制的最新发现，从 DNA 和线粒体损伤到钙稳态、自噬和细胞凋亡。特别强调活性氧的作用及其与主要信号通路的相互作用。 虽然已经开始确定新的有前途的治疗靶点和新药，但它们的疗效主要在临床前研究中得到证实，需要临床验证。 未来的研究将证实最近发现的靶点的相关性，并在更具临床相关性的模型中确定新的可药物治疗的途径，例如，人类诱导多能干细胞衍生的心肌细胞。
