Department of Molecular Pathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Mol Aspects Med. 2010 Feb;31(1):75-92. doi: 10.1016/j.mam.2009.12.003. Epub 2009 Dec 6.
Alterations in mitochondrial structure and functions have long been observed in cancer cells. Targeting mitochondria as a cancer therapeutic strategy has gained momentum in the recent years. The signaling pathways that govern mitochondrial function, apoptosis and molecules that affect mitochondrial integrity and cell viability have been important topics of the recent review in the literature. In this article, we first briefly summarize the rationale and biological basis for developing mitochondrial-targeted compounds as potential anti-cancer agents, and then provide key examples of small molecules that either directly impact mitochondria or functionally affect the metabolic alterations in cancer cells with mitochondrial dysfunction. The main focus is on the small molecular weight compounds with potential applications in cancer treatment. We also summarize information on the drug developmental stages of the key mitochondria-targeted compounds and their clinical trial status. The advantages and potential shortcomings of targeting the mitochondria for cancer treatment are also discussed.
线粒体结构和功能的改变在癌细胞中很早就被观察到。近年来,将线粒体作为癌症治疗策略的目标已经取得了进展。控制线粒体功能、凋亡的信号通路以及影响线粒体完整性和细胞活力的分子一直是文献中最近综述的重要课题。在本文中,我们首先简要总结了将靶向线粒体的化合物作为潜在抗癌药物开发的原理和生物学基础,然后提供了小分子的关键实例,这些小分子直接影响线粒体或在功能上影响具有线粒体功能障碍的癌细胞的代谢改变。主要重点是具有癌症治疗应用潜力的小分子化合物。我们还总结了关键靶向线粒体的化合物的药物开发阶段及其临床试验状况。还讨论了针对癌症治疗靶向线粒体的优点和潜在缺点。