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Amino acid metabolism as a therapeutic target in cancer: a review

Malignant cells often demonstrate a proliferative advantage when compared to non-malignant cells. However, the rapid growth and metabolism required for survival can also highlight vulnerabilities specific to these malignant cells. One such vulnerability exhibited by cancer is an increased demand for...

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Autores principales: Endicott, Molly, Jones, Michael, Hull, Jonathon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Vienna 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325646/
https://www.ncbi.nlm.nih.gov/pubmed/34292410
http://dx.doi.org/10.1007/s00726-021-03052-1
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author Endicott, Molly
Jones, Michael
Hull, Jonathon
author_facet Endicott, Molly
Jones, Michael
Hull, Jonathon
author_sort Endicott, Molly
collection PubMed
description Malignant cells often demonstrate a proliferative advantage when compared to non-malignant cells. However, the rapid growth and metabolism required for survival can also highlight vulnerabilities specific to these malignant cells. One such vulnerability exhibited by cancer is an increased demand for amino acids (AAs), which often results in a dependency on exogenous sources of AAs or requires upregulation of de novo synthesis. These metabolic alterations can be exploited by therapy, which aims to improve treatment outcome and decrease relapse and reoccurrence. One clinically utilised strategy targeting AA dependency is the use of asparaginase in the treatment of acute lymphoblastic leukaemia (ALL), which results in a depletion of exogenous asparagine and subsequent cancer cell death. Examples of other successful strategies include the exploitation of arginine deiminase and methioninase, nutrient restriction of methionine and the inhibition of glutaminase. In this review, we summarise these treatment strategies into three promising avenues: AA restriction, enzymatic depletion and inhibition of metabolism. This review provides an insight into the complexity of metabolism in cancer, whilst highlighting these three current research avenues that have support in both preclinical and clinical settings.
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spelling pubmed-83256462021-08-02 Amino acid metabolism as a therapeutic target in cancer: a review Endicott, Molly Jones, Michael Hull, Jonathon Amino Acids Review Article Malignant cells often demonstrate a proliferative advantage when compared to non-malignant cells. However, the rapid growth and metabolism required for survival can also highlight vulnerabilities specific to these malignant cells. One such vulnerability exhibited by cancer is an increased demand for amino acids (AAs), which often results in a dependency on exogenous sources of AAs or requires upregulation of de novo synthesis. These metabolic alterations can be exploited by therapy, which aims to improve treatment outcome and decrease relapse and reoccurrence. One clinically utilised strategy targeting AA dependency is the use of asparaginase in the treatment of acute lymphoblastic leukaemia (ALL), which results in a depletion of exogenous asparagine and subsequent cancer cell death. Examples of other successful strategies include the exploitation of arginine deiminase and methioninase, nutrient restriction of methionine and the inhibition of glutaminase. In this review, we summarise these treatment strategies into three promising avenues: AA restriction, enzymatic depletion and inhibition of metabolism. This review provides an insight into the complexity of metabolism in cancer, whilst highlighting these three current research avenues that have support in both preclinical and clinical settings. Springer Vienna 2021-07-22 2021 /pmc/articles/PMC8325646/ /pubmed/34292410 http://dx.doi.org/10.1007/s00726-021-03052-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Review Article
Endicott, Molly
Jones, Michael
Hull, Jonathon
Amino acid metabolism as a therapeutic target in cancer: a review
title Amino acid metabolism as a therapeutic target in cancer: a review
title_full Amino acid metabolism as a therapeutic target in cancer: a review
title_fullStr Amino acid metabolism as a therapeutic target in cancer: a review
title_full_unstemmed Amino acid metabolism as a therapeutic target in cancer: a review
title_short Amino acid metabolism as a therapeutic target in cancer: a review
title_sort amino acid metabolism as a therapeutic target in cancer: a review
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325646/
https://www.ncbi.nlm.nih.gov/pubmed/34292410
http://dx.doi.org/10.1007/s00726-021-03052-1
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