Targeting chemoresistance and mitochondria-dependent metabolic reprogramming in acute myeloid leukemia

Frontiers in Oncology

Oncology

Wenda Gao¹  Philip Y. Zhang²  Simon C. Robson³  Jinming Yu⁴  Lili Feng⁵ 

[1] Antagen Institute for Biomedical Research, Canton, MA, United States;Center for Inflammation Research, Department of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States;Center for Inflammation Research, Department of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States;Department of Medicine, Division of Gastroenterology/Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States;Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China;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;

关键词: acute myeloid leukemia;    chemoresistance;    mitochondrial metabolism;    mitotherapy;    metabolic reprogramming;   

DOI  :  10.3389/fonc.2023.1244280

 received in 2023-06-22, accepted in 2023-08-23,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Feng, Zhang, Gao, Yu and Robson