Krejčíř Radovan, Valík Dalibor, Vojtěšek Bořivoj
Klin Onkol. 2018 Winter;31(Suppl 2):14-20. doi: 10.14735/amko20182S14.
During tumor initiation and progress, cellular functions adapt to the new needs of the transformed cells and mitochondrial processes are also affected. Mitochondria are less extensively used for supplying cells with energy; rather, cancer cells utilize glycolysis to a much greater extent, even under aerobic conditions. Mitochondria produce metabolites required for cellular growth and proliferation. Mutations and alterations in gene expression of citrate cycle enzymes can directly contribute to transformation through the production of oncometabolites. The apoptotic pathway in which mitochondria play a critical role is disrupted in cancer cells, resulting in cells that do not respond to programmed cell death signaling. These differences between mitochondrial processes in healthy and diseased cells suggest they could be used in mitochondria-targeted therapies. To date, many potential molecular targets have been identified, including enzymes, signaling molecules, and membrane transporters. Even though this field has been studied for years, the first drugs, venetoclax and enasidenib, were only approved in the last two years and are the result of two different research approaches. Venetoclax targets the apoptotic pathway and enasidenib targets metabolic processes. The discovery of these two compounds demonstrates that it is possible to develop mitochondria-targeted cancer treatments.
The purpose of this article is to provide an overview of research in the field of mitochondria-targeting therapies for cancer. The main areas of research and the main approaches for treatment development are summarized. Cellular components studied as potential targets for therapy and compounds that are considered exploitable are described, as well as already approved drugs. Key words: neoplasms - molecular targeted therapy - mitochondria - antineoplastic agents - research The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Accepted: 3. 8. 2018.
在肿瘤起始和进展过程中，细胞功能会适应转化细胞的新需求，线粒体过程也会受到影响。线粒体较少用于为细胞提供能量；相反，癌细胞在更大程度上利用糖酵解，即使在有氧条件下也是如此。线粒体产生细胞生长和增殖所需的代谢产物。柠檬酸循环酶的基因突变和基因表达改变可通过产生致癌代谢物直接促进细胞转化。线粒体在其中起关键作用的凋亡途径在癌细胞中被破坏，导致细胞对程序性细胞死亡信号不产生反应。健康细胞和患病细胞线粒体过程的这些差异表明它们可用于线粒体靶向治疗。迄今为止，已确定了许多潜在的分子靶点，包括酶、信号分子和膜转运蛋白。尽管该领域已研究多年，但首批药物维奈托克和恩杂鲁胺仅在过去两年获批，且是两种不同研究方法的成果。维奈托克靶向凋亡途径，恩杂鲁胺靶向代谢过程。这两种化合物的发现表明开发线粒体靶向癌症治疗方法是可行的。
本文旨在概述癌症线粒体靶向治疗领域的研究。总结了主要研究领域和治疗开发的主要方法。描述了作为潜在治疗靶点研究的细胞成分和被认为可利用的化合物，以及已获批的药物。关键词：肿瘤 - 分子靶向治疗 - 线粒体 - 抗肿瘤药 - 研究 作者声明他们在研究中使用的药物、产品或服务方面不存在潜在利益冲突。编辑委员会声明该手稿符合国际医学期刊编辑委员会对生物医学论文的建议。接受日期：2018年8月3日。
