期刊
CANCER & METABOLISM
卷 9, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s40170-021-00253-w
关键词
Acute myeloid leukemia (AML); Mitochondria; Mitochondrial abnormalities; alterations; Mitochondrial metabolism; Mitocans; Leukemia stem cells; Synergy; Drug combinations
资金
- Cancer Prevention and Research Institute of Texas (CPRIT) [RR150044]
- NIH NIGMS [R35GM129294]
Unique mitochondrial alterations in AML cells have become a focus of research, potentially providing new treatment targets. Mitochondria are related to multiple metabolic pathways, and some mitochondria-targeting chemotherapeutics have been FDA-approved. New studies focus on revealing the effects of drugs targeting mitochondria and their potential.
Acute myeloid leukemias (AML) are a group of aggressive hematologic malignancies resulting from acquired genetic mutations in hematopoietic stem cells that affect patients of all ages. Despite decades of research, standard chemotherapy still remains ineffective for some AML subtypes and is often inappropriate for older patients or those with comorbidities. Recently, a number of studies have identified unique mitochondrial alterations that lead to metabolic vulnerabilities in AML cells that may present viable treatment targets. These include mtDNA, dependency on oxidative phosphorylation, mitochondrial metabolism, and pro-survival signaling, as well as reactive oxygen species generation and mitochondrial dynamics. Moreover, some mitochondria-targeting chemotherapeutics and their combinations with other compounds have been FDA-approved for AML treatment. Here, we review recent studies that illuminate the effects of drugs and synergistic drug combinations that target diverse biomolecules and metabolic pathways related to mitochondria and their promise in experimental studies, clinical trials, and existing chemotherapeutic regimens.
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