Journal
DRUG DISCOVERY TODAY
Volume 26, Issue 3, Pages 817-825Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2020.12.006
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Funding
- National Natural Science Foundation of China [81922064, 81970481, 81903502, 82000514]
- National Major Scientific and Technological Special Project for 'Significant New Drugs Development' [2018ZX09201018-021]
- Sichuan Science and Technology Program [2019YFS0003]
- CAMS Innovation Fund for Medical Science [2019-RC-HL-023]
- Scientific Research Project, Health Commission of Sichuan Province [20PJ002]
- National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University [Z20201004]
- Post-Doctor Research Project, West China Hospital, Sichuan University [2019HXBH034]
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Folate-mediated one-carbon metabolism plays a vital role in cancer development, with folate-metabolizing enzymes SHMT2 and MTHFD2 being associated with the progression of cancers and showing potential for tumor-targeted therapy.
Folate-mediated one-carbon metabolism (FOCM) supports vital events for the growth and survival of proliferating cells. Nucleotide synthesis and DNA methylation are the biochemical bases of cancers that are highly dependent on FOCM. Recent studies revealed that FOCM is connected with redox homeostasis and epigenetics in cancer. Furthermore, folate-metabolizing enzymes, such as serine hydroxymethyltransferase 2 (SHMT2) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), are associated with the development of cancers, including breast cancer, highlighting their potential application in tumor-targeted therapy. Therefore, targeting metabolizing enzymes, especially SHMT2 and MTHFD2, provides a novel strategy for cancer treatment. In this review, we outline current understanding of the functions of SHMT2 and MTHFD2, discussing their expression, potential functions, and regulatory mechanism in cancers. Furthermore, we discuss examples of inhibitors of SHMT2 and MTHFD2.
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