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Contribution of uric acid to cancer risk, recurrence, and mortality

Two risk factors for the development and progression of cancers that are amenable to life style modification are chronic inflammation and the metabolic syndrome. This review proposes two new targets that may mechanistically integrate inflammation and metabolic syndrome, have been largely ignored, an...

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Autores principales: Fini, Mehdi A, Elias, Anthony, Johnson, Richard J, Wright, Richard M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560981/
https://www.ncbi.nlm.nih.gov/pubmed/23369448
http://dx.doi.org/10.1186/2001-1326-1-16
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author Fini, Mehdi A
Elias, Anthony
Johnson, Richard J
Wright, Richard M
author_facet Fini, Mehdi A
Elias, Anthony
Johnson, Richard J
Wright, Richard M
author_sort Fini, Mehdi A
collection PubMed
description Two risk factors for the development and progression of cancers that are amenable to life style modification are chronic inflammation and the metabolic syndrome. This review proposes two new targets that may mechanistically integrate inflammation and metabolic syndrome, have been largely ignored, and are known to be druggable. Recent evidence has demonstrated that elevated serum uric acid (hyperuricemia) is associated with excess cancer risk, recurrence, and mortality. Although uric acid (UA) can function as a systemic antioxidant, its pro-inflammatory properties have been postulated to play an important role in the pathogenesis of cancer. Furthermore, obesity, Type 2 Diabetes Mellitus (T2DM), and the metabolic syndrome (MetS) are also associated with excess cancer, chronic inflammation, and with hyperuricemia, suggesting that UA may represent an important link between these disorders and the development of cancer. While pharmacological modulation of hyperuricemia could in principal augment anti-cancer therapeutic strategies, some cancer cells express low intracellular levels of the enzyme Xanthine Oxidoreductase (XOR) that are associated with increased cancer aggressiveness and poor clinical outcome. Thus, systemic pharmacological inhibition of XOR may worsen clinical outcome, and specific strategies that target serum uric acid (SUA) without inhibiting tumor cell XOR may create new therapeutic opportunities for cancer associated with hyperuricemia. This review will summarize the evidence that elevated SUA may be a true risk factor for cancer incidence and mortality, and mechanisms by which UA may contribute to cancer pathogenesis will be discussed in the hope that these will identify new opportunities for cancer management.
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spelling pubmed-35609812013-02-04 Contribution of uric acid to cancer risk, recurrence, and mortality Fini, Mehdi A Elias, Anthony Johnson, Richard J Wright, Richard M Clin Transl Med Review Two risk factors for the development and progression of cancers that are amenable to life style modification are chronic inflammation and the metabolic syndrome. This review proposes two new targets that may mechanistically integrate inflammation and metabolic syndrome, have been largely ignored, and are known to be druggable. Recent evidence has demonstrated that elevated serum uric acid (hyperuricemia) is associated with excess cancer risk, recurrence, and mortality. Although uric acid (UA) can function as a systemic antioxidant, its pro-inflammatory properties have been postulated to play an important role in the pathogenesis of cancer. Furthermore, obesity, Type 2 Diabetes Mellitus (T2DM), and the metabolic syndrome (MetS) are also associated with excess cancer, chronic inflammation, and with hyperuricemia, suggesting that UA may represent an important link between these disorders and the development of cancer. While pharmacological modulation of hyperuricemia could in principal augment anti-cancer therapeutic strategies, some cancer cells express low intracellular levels of the enzyme Xanthine Oxidoreductase (XOR) that are associated with increased cancer aggressiveness and poor clinical outcome. Thus, systemic pharmacological inhibition of XOR may worsen clinical outcome, and specific strategies that target serum uric acid (SUA) without inhibiting tumor cell XOR may create new therapeutic opportunities for cancer associated with hyperuricemia. This review will summarize the evidence that elevated SUA may be a true risk factor for cancer incidence and mortality, and mechanisms by which UA may contribute to cancer pathogenesis will be discussed in the hope that these will identify new opportunities for cancer management. Springer 2012-08-15 /pmc/articles/PMC3560981/ /pubmed/23369448 http://dx.doi.org/10.1186/2001-1326-1-16 Text en Copyright ©2012 Fini et al.; licensee Springer. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Fini, Mehdi A
Elias, Anthony
Johnson, Richard J
Wright, Richard M
Contribution of uric acid to cancer risk, recurrence, and mortality
title Contribution of uric acid to cancer risk, recurrence, and mortality
title_full Contribution of uric acid to cancer risk, recurrence, and mortality
title_fullStr Contribution of uric acid to cancer risk, recurrence, and mortality
title_full_unstemmed Contribution of uric acid to cancer risk, recurrence, and mortality
title_short Contribution of uric acid to cancer risk, recurrence, and mortality
title_sort contribution of uric acid to cancer risk, recurrence, and mortality
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560981/
https://www.ncbi.nlm.nih.gov/pubmed/23369448
http://dx.doi.org/10.1186/2001-1326-1-16
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