University of Chicago, Department of Medicine, Section of Hematology/Oncology , 5841 S. Maryland Avenue, MC 2115 Chicago, IL 60637 , USA +1 773 702 4399 ; +1 773 834 1798 ;
Expert Opin Investig Drugs. 2014 May;23(5):675-92. doi: 10.1517/13543784.2014.899350. Epub 2014 Mar 22.
Lung cancer mortality rates remain at unacceptably high levels. Although mitochondrial dysfunction is a characteristic of most tumor types, mitochondrial dynamics are often overlooked. Altered rates of mitochondrial fission and fusion are observed in lung cancer and can influence metabolic function, proliferation and cell survival.
In this review, the authors outline the mechanisms of mitochondrial fission and fusion. They also identify key regulatory proteins and highlight the roles of fission and fusion in metabolism and other cellular functions (e.g., proliferation, apoptosis) with an emphasis on lung cancer and the interaction with known cancer biomarkers. They also examine the current therapeutic strategies reported as altering mitochondrial dynamics and review emerging mitochondria-targeted therapies.
Mitochondrial dynamics are an attractive target for therapeutic intervention in lung cancer. Mitochondrial dysfunction, despite its molecular heterogeneity, is a common abnormality of lung cancer. Targeting mitochondrial dynamics can alter mitochondrial metabolism, and many current therapies already non-specifically affect mitochondrial dynamics. A better understanding of mitochondrial dynamics and their interaction with currently identified cancer 'drivers' such as Kirsten-Rat Sarcoma Viral Oncogene homolog will lead to the development of novel therapeutics.
肺癌死亡率仍处于不可接受的高水平。虽然线粒体功能障碍是大多数肿瘤类型的特征，但线粒体动力学常常被忽视。在肺癌中观察到线粒体分裂和融合的速率发生改变，这会影响代谢功能、增殖和细胞存活。
在这篇综述中，作者概述了线粒体分裂和融合的机制。他们还确定了关键的调节蛋白，并强调了分裂和融合在代谢和其他细胞功能（如增殖、凋亡）中的作用，重点介绍了肺癌以及与已知癌症生物标志物的相互作用。他们还研究了目前报道的改变线粒体动力学的治疗策略，并综述了新兴的线粒体靶向治疗。
线粒体动力学是肺癌治疗干预的一个有吸引力的靶点。尽管存在分子异质性，但线粒体功能障碍是肺癌的常见异常。靶向线粒体动力学可以改变线粒体代谢，许多当前的治疗方法已经非特异性地影响线粒体动力学。更好地了解线粒体动力学及其与目前确定的癌症“驱动因素”（如 Kirsten-Rat Sarcoma Viral Oncogene homolog）的相互作用将导致新的治疗方法的发展。
