The mitochondrial arm of the one-carbon pathway, which is essential for nucleotide synthesis, becomes dominant in cancer cells due to overexpression of several enzymes of the pathway, including MTHFD2. A study now reports on a high-affinity inhibitor of MTHFD2 that starves cancer cells of DNA building blocks and shows potential for selective tumor targeting.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Niederhuber, J.E., Armitage, J.O., Doroshow, J.H., Kastan, M.B. & Tepper, J.E. Abeloff’s Clinical Oncology 6th edn. (Elsevier, 2020).
Zhao, L. N. et al. Oncogene 40, 2339–2354 (2021).
Ducker, G. S. & Rabinowitz, J. D. Cell Metab. 25, 27–42 (2016).
Nilsson, R. et al. Nat. Commun. 5, 3128 (2014).
Bonagas, N. et al. Nat. Can. https://doi.org/10.1038/s43018-022-00331-y (2022).
Ducker, G. S. et al. Cell Metab. 23, 1140–1153 (2016).
Temple, C. Jr et al. J. Med. Chem. 25, 161–166 (1982).
Tonkinson, J. L. et al. J. Pharmacol. Exp. Ther. 287, 315–321 (1998).
Schmidt, A. et al. Biochemistry 39, 6325–6335 (2000).
Eadsforth, T. C., Maluf, F. V. & Hunter, W. N. FEBS J. 279, 4350–4360 (2012).
Gustafsson, R. et al. Cancer Res. 77, 937–948 (2017).
Ju, H. Q. et al. J. Natl. Cancer Inst. 111, 584–596 (2019).
Pikman, Y. et al. J. Exp. Med. 213, 1285–1306 (2016).
Kawai, J. et al. J. Med. Chem. 62, 10204–10220 (2019).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
T.D.H. is the chief scientific officer of FoRx Therapeutics, a company that develops drugs for the treatment of cancer.
Rights and permissions
About this article
Cite this article
Dionellis, V.S., Halazonetis, T.D. Beating cancer one carbon at a time. Nat Cancer 3, 141–142 (2022). https://doi.org/10.1038/s43018-022-00333-w
Published:
Issue Date:
DOI: https://doi.org/10.1038/s43018-022-00333-w
