Feng Lili, Zhang Philip Y, Gao Wenda, Yu Jinming, Robson Simon C
Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Center for Inflammation Research, Department of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Front Oncol. 2023 Sep 7;13:1244280. doi: 10.3389/fonc.2023.1244280. eCollection 2023.
Chemoresistance often complicates the management of cancer, as noted in the instance of acute myeloid leukemia (AML). Mitochondrial function is considered important for the viability of AML blasts and appears to also modulate chemoresistance. As mitochondrial metabolism is aberrant in AML, any distinct pathways could be directly targeted to impact both cell viability and chemoresistance. Therefore, identifying and targeting those precise rogue elements of mitochondrial metabolism could be a valid therapeutic strategy in leukemia. Here, we review the evidence for abnormalities in mitochondria metabolic processes in AML cells, that likely impact chemoresistance. We further address several therapeutic approaches targeting isocitrate dehydrogenase 2 (IDH2), CD39, nicotinamide phosphoribosyl transferase (NAMPT), electron transport chain (ETC) complex in AML and also consider the roles of mesenchymal stromal cells. We propose the term "mitotherapy" to collectively refer to such regimens that attempt to override mitochondria-mediated metabolic reprogramming, as used by cancer cells. Mounting evidence suggests that mitotherapy could provide a complementary strategy to overcome chemoresistance in liquid cancers, as well as in solid tumors.
正如急性髓系白血病（AML）的情况所示，化疗耐药常常使癌症治疗变得复杂。线粒体功能被认为对AML原始细胞的生存能力很重要，而且似乎还能调节化疗耐药性。由于AML中的线粒体代谢异常，任何独特的途径都可以直接作为靶点来影响细胞生存能力和化疗耐药性。因此，识别并靶向线粒体代谢中那些精确的异常成分可能是白血病的一种有效治疗策略。在此，我们综述了AML细胞中线粒体代谢过程异常的证据，这些异常可能影响化疗耐药性。我们进一步探讨了针对AML中异柠檬酸脱氢酶2（IDH2）、CD39、烟酰胺磷酸核糖转移酶（NAMPT）、电子传递链（ETC）复合物的几种治疗方法，并考虑了间充质基质细胞的作用。我们提出“线粒体疗法”这一术语，用以统称那些试图推翻癌细胞所采用的线粒体介导的代谢重编程的治疗方案。越来越多的证据表明，线粒体疗法可以作为一种补充策略，用于克服液体癌症以及实体瘤中的化疗耐药性。
