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Can small molecular inhibitors that stop de novo serine synthesis be used in cancer treatment?

To sustain their malignancy, tumour cells acquire several metabolic adaptations such as increased oxygen, glucose, glutamine, and lipids uptake. Other metabolic processes are also enhanced as part of tumour metabolic reprogramming, for example, increased serine metabolism. Serine is a non-essential...

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Autores principales: McNamee, Megan Jessica, Michod, David, Niklison-Chirou, Maria Victoria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087698/
https://www.ncbi.nlm.nih.gov/pubmed/33931592
http://dx.doi.org/10.1038/s41420-021-00474-4
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author McNamee, Megan Jessica
Michod, David
Niklison-Chirou, Maria Victoria
author_facet McNamee, Megan Jessica
Michod, David
Niklison-Chirou, Maria Victoria
author_sort McNamee, Megan Jessica
collection PubMed
description To sustain their malignancy, tumour cells acquire several metabolic adaptations such as increased oxygen, glucose, glutamine, and lipids uptake. Other metabolic processes are also enhanced as part of tumour metabolic reprogramming, for example, increased serine metabolism. Serine is a non-essential amino acid that supports several metabolic processes that are crucial for the growth and survival of proliferating cells, including protein, DNA, and glutathione synthesis. Indeed, increased activity of D-3-phosphoglycerate dehydrogenase (PHGDH), the enzyme rate-limiting de novo serine synthesis, has been extensively reported in several tumours. Therefore, selective inhibition of PHGDH may represent a new therapeutic strategy for over-expressing PHGDH tumours, owing to its downstream inhibition of essential biomass production such as one-carbon units and nucleotides. This perspective article will discuss the current status of research into small molecular inhibitors against PHGDH in colorectal cancer, breast cancer, and Ewing’s sarcoma. We will summarise recent studies on the development of PHGDH-inhibitors, highlighting their clinical potential as new therapeutics. It also wants to shed a light on some of the key limitations of the use of PHGDH-inhibitors in cancer treatment which are worth taking into account.
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spelling pubmed-80876982021-05-05 Can small molecular inhibitors that stop de novo serine synthesis be used in cancer treatment? McNamee, Megan Jessica Michod, David Niklison-Chirou, Maria Victoria Cell Death Discov Perspective To sustain their malignancy, tumour cells acquire several metabolic adaptations such as increased oxygen, glucose, glutamine, and lipids uptake. Other metabolic processes are also enhanced as part of tumour metabolic reprogramming, for example, increased serine metabolism. Serine is a non-essential amino acid that supports several metabolic processes that are crucial for the growth and survival of proliferating cells, including protein, DNA, and glutathione synthesis. Indeed, increased activity of D-3-phosphoglycerate dehydrogenase (PHGDH), the enzyme rate-limiting de novo serine synthesis, has been extensively reported in several tumours. Therefore, selective inhibition of PHGDH may represent a new therapeutic strategy for over-expressing PHGDH tumours, owing to its downstream inhibition of essential biomass production such as one-carbon units and nucleotides. This perspective article will discuss the current status of research into small molecular inhibitors against PHGDH in colorectal cancer, breast cancer, and Ewing’s sarcoma. We will summarise recent studies on the development of PHGDH-inhibitors, highlighting their clinical potential as new therapeutics. It also wants to shed a light on some of the key limitations of the use of PHGDH-inhibitors in cancer treatment which are worth taking into account. Nature Publishing Group UK 2021-04-30 /pmc/articles/PMC8087698/ /pubmed/33931592 http://dx.doi.org/10.1038/s41420-021-00474-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Perspective
McNamee, Megan Jessica
Michod, David
Niklison-Chirou, Maria Victoria
Can small molecular inhibitors that stop de novo serine synthesis be used in cancer treatment?
title Can small molecular inhibitors that stop de novo serine synthesis be used in cancer treatment?
title_full Can small molecular inhibitors that stop de novo serine synthesis be used in cancer treatment?
title_fullStr Can small molecular inhibitors that stop de novo serine synthesis be used in cancer treatment?
title_full_unstemmed Can small molecular inhibitors that stop de novo serine synthesis be used in cancer treatment?
title_short Can small molecular inhibitors that stop de novo serine synthesis be used in cancer treatment?
title_sort can small molecular inhibitors that stop de novo serine synthesis be used in cancer treatment?
topic Perspective
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087698/
https://www.ncbi.nlm.nih.gov/pubmed/33931592
http://dx.doi.org/10.1038/s41420-021-00474-4
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