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新型线粒体靶向药物在癌症治疗中的应用

Novel Mitochondria-targeted Drugs for Cancer Therapy.

机构信息

Department of Physiology, Faculty of Medicine, Masaryk University / Kamenice 5, CZ-625 00 Brno, Czech Republic.

Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, CZ-121 08 Prague, Czech Republic.

出版信息

Mini Rev Med Chem. 2021;21(7):816-832. doi: 10.2174/1389557520666201118153242.

Abstract

The search for mitochondria-targeted drugs has dramatically risen over the last decade. Mitochondria are essential organelles serving not only as a powerhouse of the cell but also as a key player in cell proliferation and cell death. Their central role in the energetic metabolism, calcium homeostasis and apoptosis makes them an intriguing field of interest for cancer pharmacology. In cancer cells, many mitochondrial signaling and metabolic pathways are altered. These changes contribute to cancer development and progression. Due to changes in mitochondrial metabolism and changes in membrane potential, cancer cells are more susceptible to mitochondria-targeted therapy. The loss of functional mitochondria leads to the arrest of cancer progression and/or a cancer cell death. Identification of mitochondrial changes specific for tumor growth and progression, rational development of new mitochondria-targeted drugs and research on delivery agents led to the advance of this promising area. This review will highlight the current findings in mitochondrial biology, which are important for cancer initiation, progression and resistance, and discuss approaches of cancer pharmacology with a special focus on the anti-cancer drugs referred to as 'mitocans'.

摘要

在过去的十年中,针对线粒体靶向药物的研究急剧增加。线粒体是细胞器的重要组成部分,不仅是细胞的动力源,也是细胞增殖和细胞死亡的关键参与者。它们在能量代谢、钙稳态和细胞凋亡中的核心作用使它们成为癌症药理学中一个有趣的研究领域。在癌细胞中,许多线粒体信号和代谢途径发生改变。这些变化促进了癌症的发展和进展。由于线粒体代谢的改变和膜电位的改变,癌细胞更容易受到线粒体靶向治疗的影响。功能性线粒体的丧失导致癌症进展的停滞和/或癌细胞死亡。鉴定出肿瘤生长和进展特异性的线粒体变化,合理开发新的线粒体靶向药物,并研究递药载体,这些都推动了这一极具前景的领域的发展。本文将重点介绍与癌症起始、进展和耐药性相关的线粒体生物学的最新发现,并讨论癌症药理学的方法,特别关注被称为“mitocans”的抗癌药物。

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