Cui Qingbin, Wen Shijun, Huang Peng
Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Future Med Chem. 2017 Jun;9(9):929-949. doi: 10.4155/fmc-2017-0011. Epub 2017 Jun 21.
Mitochondria play a key role in ATP generation, redox homeostasis and regulation of apoptosis. Due to the essential role of mitochondria in metabolism and cell survival, targeting mitochondria in cancer cells is considered as an attractive therapeutic strategy. However, metabolic flexibility in cancer cells may enable the upregulation of compensatory pathways, such as glycolysis to support cancer cell survival when mitochondrial metabolism is inhibited. Thus, compounds capable of both targeting mitochondria and inhibiting glycolysis may be particularly useful to overcome such drug-resistant mechanism. This review provides an update on recent development in the field of targeting mitochondria and novel compounds that impact mitochondria, glycolysis or both. Key challenges in this research area and potential solutions are also discussed.
线粒体在三磷酸腺苷(ATP)生成、氧化还原稳态及细胞凋亡调控中发挥关键作用。由于线粒体在新陈代谢和细胞存活中具有重要作用,因此将癌细胞中的线粒体作为靶点被视为一种颇具吸引力的治疗策略。然而,癌细胞的代谢灵活性可能会促使补偿途径上调,比如在抑制线粒体代谢时通过糖酵解来维持癌细胞存活。因此,能够同时靶向线粒体并抑制糖酵解的化合物对于克服这种耐药机制可能特别有用。本综述介绍了靶向线粒体领域的最新进展以及影响线粒体、糖酵解或两者的新型化合物。还讨论了该研究领域的关键挑战及潜在解决方案。