Folate metabolism: a re-emerging therapeutic target in haematological cancers

Zarou, M.-M., Vazquez, A. and Helgason, G. V. (2021) Folate metabolism: a re-emerging therapeutic target in haematological cancers. Leukemia, 35(6), pp. 1539-1551. (doi: 10.1038/s41375-021-01189-2) (PMID:33707653)

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Folate-mediated one carbon (1C) metabolism supports a series of processes that are essential for the cell. Through a number of interlinked reactions happening in the cytosol and mitochondria of the cell, folate metabolism contributes to de novo purine and thymidylate synthesis, to the methionine cycle and redox defence. Targeting the folate metabolism gave rise to modern chemotherapy, through the introduction of antifolates to treat paediatric leukaemia. Since then, antifolates, such as methotrexate and pralatrexate have been used to treat a series of blood cancers in clinic. However, traditional antifolates have many deleterious side effects in normal proliferating tissue, highlighting the urgent need for novel strategies to more selectively target 1C metabolism. Notably, mitochondrial 1C enzymes have been shown to be significantly upregulated in various cancers, making them attractive targets for the development of new chemotherapeutic agents. In this article, we present a detailed overview of folate-mediated 1C metabolism, its importance on cellular level and discuss how targeting folate metabolism has been exploited in blood cancers. Additionally, we explore possible therapeutic strategies that could overcome the limitations of traditional antifolates.

Item Type:Articles
Additional Information:The work was supported by Cancer Research UK Glasgow Centre (A25142).
Glasgow Author(s) Enlighten ID:Vazquez, Alexei and Zarou, Martha-Maria and Helgason, Professor Vignir
Authors: Zarou, M.-M., Vazquez, A., and Helgason, G. V.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Leukemia
Publisher:Springer Nature
ISSN (Online):1476-5551
Published Online:11 March 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Leukemia 35(6): 1539-1551
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
174115CRUK Centre RenewalOwen SansomCancer Research UK (CRUK)C7932/A25142CS - Beatson Institute for Cancer Research