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Emerging roles for UDP-glucuronosyltransferases in drug resistance and cancer progression
The best-known role of UDP-glucuronosyltransferase enzymes (UGTs) in cancer is the metabolic inactivation of drug therapies. By conjugating glucuronic acid to lipophilic drugs, UGTs impair the biological activity and enhance the water solubility of these agents, driving their elimination. Multiple c...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188667/ https://www.ncbi.nlm.nih.gov/pubmed/32047295 http://dx.doi.org/10.1038/s41416-019-0722-0 |
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author | Allain, Eric P. Rouleau, Michèle Lévesque, Eric Guillemette, Chantal |
author_facet | Allain, Eric P. Rouleau, Michèle Lévesque, Eric Guillemette, Chantal |
author_sort | Allain, Eric P. |
collection | PubMed |
description | The best-known role of UDP-glucuronosyltransferase enzymes (UGTs) in cancer is the metabolic inactivation of drug therapies. By conjugating glucuronic acid to lipophilic drugs, UGTs impair the biological activity and enhance the water solubility of these agents, driving their elimination. Multiple clinical observations support an expanding role for UGTs as modulators of the drug response and in mediating drug resistance in numerous cancer types. However, accumulating evidence also suggests an influence of the UGT pathway on cancer progression. Dysregulation of the expression and activity of UGTs has been associated with the progression of several cancers, arguing for UGTs as possible mediators of oncogenic pathways and/or disease accelerators in a drug-naive context. The consequences of altered UGT activity on tumour biology are incompletely understood. They might be associated with perturbed levels of bioactive endogenous metabolites such as steroids and bioactive lipids that are inactivated by UGTs or through non-enzymatic mechanisms, thereby eliciting oncogenic signalling cascades. This review highlights the evidence supporting dual roles for the UGT pathway, affecting cancer progression and drug resistance. Pharmacogenomic testing of UGT profiles in patients and the development of therapeutic options that impair UGT actions could provide useful prognostic and predictive biomarkers and enhance the efficacy of anti-cancer drugs. |
format | Online Article Text |
id | pubmed-7188667 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-71886672020-05-04 Emerging roles for UDP-glucuronosyltransferases in drug resistance and cancer progression Allain, Eric P. Rouleau, Michèle Lévesque, Eric Guillemette, Chantal Br J Cancer Review Article The best-known role of UDP-glucuronosyltransferase enzymes (UGTs) in cancer is the metabolic inactivation of drug therapies. By conjugating glucuronic acid to lipophilic drugs, UGTs impair the biological activity and enhance the water solubility of these agents, driving their elimination. Multiple clinical observations support an expanding role for UGTs as modulators of the drug response and in mediating drug resistance in numerous cancer types. However, accumulating evidence also suggests an influence of the UGT pathway on cancer progression. Dysregulation of the expression and activity of UGTs has been associated with the progression of several cancers, arguing for UGTs as possible mediators of oncogenic pathways and/or disease accelerators in a drug-naive context. The consequences of altered UGT activity on tumour biology are incompletely understood. They might be associated with perturbed levels of bioactive endogenous metabolites such as steroids and bioactive lipids that are inactivated by UGTs or through non-enzymatic mechanisms, thereby eliciting oncogenic signalling cascades. This review highlights the evidence supporting dual roles for the UGT pathway, affecting cancer progression and drug resistance. Pharmacogenomic testing of UGT profiles in patients and the development of therapeutic options that impair UGT actions could provide useful prognostic and predictive biomarkers and enhance the efficacy of anti-cancer drugs. Nature Publishing Group UK 2020-02-12 2020-04-28 /pmc/articles/PMC7188667/ /pubmed/32047295 http://dx.doi.org/10.1038/s41416-019-0722-0 Text en © The Author(s) 2020 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 | Review Article Allain, Eric P. Rouleau, Michèle Lévesque, Eric Guillemette, Chantal Emerging roles for UDP-glucuronosyltransferases in drug resistance and cancer progression |
title | Emerging roles for UDP-glucuronosyltransferases in drug resistance and cancer progression |
title_full | Emerging roles for UDP-glucuronosyltransferases in drug resistance and cancer progression |
title_fullStr | Emerging roles for UDP-glucuronosyltransferases in drug resistance and cancer progression |
title_full_unstemmed | Emerging roles for UDP-glucuronosyltransferases in drug resistance and cancer progression |
title_short | Emerging roles for UDP-glucuronosyltransferases in drug resistance and cancer progression |
title_sort | emerging roles for udp-glucuronosyltransferases in drug resistance and cancer progression |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188667/ https://www.ncbi.nlm.nih.gov/pubmed/32047295 http://dx.doi.org/10.1038/s41416-019-0722-0 |
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