Department of Pharmacology, Campbell University Jerry Wallace School of Osteopathic Medicine, Buies Creek, NC, 27560, USA.
Department of Biochemistry, Duquesne University College of Osteopathic Medicine, Pittsburgh, PA, 15282, USA.
Mol Cell Biochem. 2024 May;479(5):1121-1132. doi: 10.1007/s11010-023-04783-3. Epub 2023 Jun 13.
Doxorubicin (Dox) is among the most widely used cancer chemotherapeutic drugs. The clinical use of Dox is, however, limited due to its cardiotoxicity. Studies over the past several decades have suggested various mechanisms of Dox-induced cardiotoxicity (DIC). Among them are oxidative stress, topoisomerase inhibition, and mitochondrial damage. Several novel molecular targets and signaling pathways underlying DIC have emerged over the past few years. The most notable advances include discovery of ferroptosis as a major form of cell death in Dox cytotoxicity, and elucidation of the involvement of cardiogenetics and regulatory RNAs as well as multiple other targets in DIC. In this review, we discuss these advances, focusing on latest cutting-edge research discoveries from mechanistic studies reported in influential journals rather than surveying all research studies available in the literature.
多柔比星（Dox）是最广泛使用的癌症化疗药物之一。然而，由于其心脏毒性，Dox 的临床应用受到限制。过去几十年的研究提出了多种多柔比星诱导的心脏毒性（DIC）机制。其中包括氧化应激、拓扑异构酶抑制和线粒体损伤。过去几年出现了几个新的 DIC 潜在分子靶点和信号通路。最显著的进展包括发现铁死亡是 Dox 细胞毒性中主要的细胞死亡形式，以及阐明心脏遗传学和调节 RNA 以及 DIC 中的其他多个靶点的参与。在这篇综述中，我们讨论了这些进展，重点介绍了在有影响力的期刊上报道的机制研究中最新的前沿研究发现，而不是调查文献中所有可用的研究。
