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Targeting MTHFD2 to Exploit Cancer-Specific Metabolism and the DNA Damage Response
Louise Ramos1,2, Martin Henriksson3, Thomas Helleday1,3
1Weston Park Cancer Centre and Division of Clinical Medicine, School of Medicine and Population Health, Faculty of Health, University of Sheffield, Sheffield, United Kingdom.
Abstract:
The one-carbon folate enzyme methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2 (MTHFD2) is a promising therapeutic target in cancer. MTHFD2 is upregulated across numerous cancer types, promotes growth and metastasis of cancer, and correlates with poorer survival. Recent studies have developed small-molecule inhibitors to the isozymes MTHFD2 and MTHFD1 that show promise as anticancer agents through different mechanisms. This review discusses the current understanding of the function of MTHFD2 in cancer and the status of inhibitors for treating MTHFD2-overexpressing cancers.
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