School of Medical Science, Griffith University, Southport, Qld, Australia.
Mitochondrion. 2013 May;13(3):199-208. doi: 10.1016/j.mito.2012.07.112. Epub 2012 Jul 28.
Mitochondria have emerged as an intriguing target for anti-cancer drugs, inherent to vast majority if not all types of tumours. Drugs that target mitochondria and exert anti-cancer activity have become a focus of recent research due to their great clinical potential (which has not been harnessed thus far). The exceptional potential of mitochondria as a target for anti-cancer agents has been reinforced by the discouraging finding that even tumours of the same type from individual patients differ in a number of mutations. This is consistent with the idea of personalised therapy, an elusive goal at this stage, in line with the notion that tumours are unlikely to be treated by agents that target only a single gene or a single pathway. This endows mitochondria, an invariant target present in all tumours, with an exceptional momentum. This train of thoughts inspired us to define a class of anti-cancer drugs acting by way of mitochondrial 'destabilisation', termed 'mitocans'. In this communication, we define mitocans (many of which have been known for a long time) and classify them into several classes based on their molecular mode of action. We chose the targets that are of major importance from the point of view of their role in mitochondrial destabilisation by small compounds, some of which are now trialled as anti-cancer agents. The classification starts with targets at the surface of mitochondria and ending up with those in the mitochondrial matrix. The purpose of this review is to present in a concise manner the classification of compounds that hold a considerable promise as potential anti-cancer drugs.
线粒体已成为抗癌药物的一个有趣靶点，几乎存在于绝大多数（如果不是所有）类型的肿瘤中。由于其巨大的临床潜力（迄今为止尚未被利用），靶向线粒体并具有抗癌活性的药物已成为近期研究的焦点。由于令人沮丧的发现，即使来自个体患者的同一类型的肿瘤在许多突变方面存在差异，因此将线粒体作为抗癌药物靶点的特殊潜力得到了加强。这与个性化治疗的理念一致，这是现阶段难以实现的目标，与肿瘤不太可能通过仅靶向单个基因或单个途径的药物治疗的观点一致。这使线粒体成为一个不变的靶点，赋予了它特殊的动力。这种思路启发我们定义了一类通过线粒体“不稳定化”作用的抗癌药物，称为“mitocans”。在本通讯中，我们定义了 mitocans（其中许多已经存在了很长时间），并根据它们在小分子诱导线粒体不稳定化方面的分子作用模式将它们分为几类。我们选择了从小分子诱导线粒体不稳定化的角度来看非常重要的靶点，其中一些目前正在作为抗癌药物进行试验。分类从线粒体表面的靶点开始，一直到线粒体基质中的靶点。本文的目的是简明扼要地介绍作为潜在抗癌药物具有相当前景的化合物的分类。
