期刊
MOLECULAR CANCER THERAPEUTICS
卷 19, 期 11, 页码 2245-2255出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1535-7163.MCT-20-0423
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资金
- NIH [R01 CA53535, R01 CA152316, R01 CA166711]
- Barbara Ann Karmanos Cancer Institute
- Eunice and Milton Ring Endowed Chair for Cancer Research
- Duquesne University Adrian Van Kaam Chair in Scholarly Excellence
- [T32 CA009531]
- [F30 CA228221]
One-carbon (1C) metabolism encompasses folate-mediated 1C transfer reactions and related processes, including nucleotide and amino acid biosynthesis, antioxidant regeneration, and epigenetic regulation. 1C pathways are compartmentalized in the cytosol, mitochondria, and nucleus. 1C metabolism in the cytosol has been an important therapeutic target for cancer since the inception of modern chemotherapy, and antifolates targeting cytosolic 1C pathways continue to be a mainstay of the chemotherapy armamentarium for cancer. Recent insights into the complexities of 1C metabolism in cancer cells, including the critical role of the mitochondrial 1C pathway as a source of 1C units, glycine, reducing equivalents, and ATP, have spurred the discovery of novel compounds that target these reactions, with particular focus on 5,10-methylene tetrahydrofolate dehydrogenase 2 and serine hydroxy-methyltransferase 2. In this review, we discuss key aspects of 1C metabolism, with emphasis on the importance of mitochondrial 1C metabolism to metabolic homeostasis, its relationship with the oncogenic phenotype, and its therapeutic potential for cancer.
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