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1-C Metabolism-Serine, Glycine, Folates-In Acute Myeloid Leukemia

期刊

PHARMACEUTICALS
卷 14, 期 3, 页码 -

出版社

MDPI
DOI: 10.3390/ph14030190

关键词

amino acid metabolism; cancer therapy; leukemia; amino-acid-degrading enzymes; amino acid restriction in cancer

资金

  1. University of Maryland Greenebaum Comprehensive Cancer Center Support grant [P30CA134274]

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Metabolic reprogramming contributes to tumor development and leads to metabolic vulnerabilities that can be targeted in cancer treatment. Alterations in fatty acid, folate, and amino acid metabolism pathways have been identified in hematological malignancies, providing new opportunities for developing novel cancer therapies targeting these pathways. Glutamine depletion and inhibition of the one-carbon metabolism are also being explored as potential therapeutic strategies for cancers dependent on these metabolic processes.
Metabolic reprogramming contributes to tumor development and introduces metabolic liabilities that can be exploited to treat cancer. Studies in hematological malignancies have shown alterations in fatty acid, folate, and amino acid metabolism pathways in cancer cells. One-carbon (1-C) metabolism is essential for numerous cancer cell functions, including protein and nucleic acid synthesis and maintaining cellular redox balance, and inhibition of the 1-C pathway has yielded several highly active drugs, such as methotrexate and 5-FU. Glutamine depletion has also emerged as a therapeutic approach for cancers that have demonstrated dependence on glutamine for survival. Recent studies have shown that in response to glutamine deprivation leukemia cells upregulate key enzymes in the serine biosynthesis pathway, suggesting that serine upregulation may be a targetable compensatory mechanism. These new findings may provide opportunities for novel cancer treatments.

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