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Defining a metabolic landscape of tumours: genome meets metabolism

Cancer is a complex disease of multiple alterations occuring at the epigenomic, genomic, transcriptomic, proteomic and/or metabolic levels. The contribution of genetic mutations in cancer initiation, progression and evolution is well understood. However, although metabolic changes in cancer have lon...

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Autores principales: Seth Nanda, Chandan, Venkateswaran, Sharavan Vishaan, Patani, Neill, Yuneva, Mariia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051970/
https://www.ncbi.nlm.nih.gov/pubmed/31819196
http://dx.doi.org/10.1038/s41416-019-0663-7
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author Seth Nanda, Chandan
Venkateswaran, Sharavan Vishaan
Patani, Neill
Yuneva, Mariia
author_facet Seth Nanda, Chandan
Venkateswaran, Sharavan Vishaan
Patani, Neill
Yuneva, Mariia
author_sort Seth Nanda, Chandan
collection PubMed
description Cancer is a complex disease of multiple alterations occuring at the epigenomic, genomic, transcriptomic, proteomic and/or metabolic levels. The contribution of genetic mutations in cancer initiation, progression and evolution is well understood. However, although metabolic changes in cancer have long been acknowledged and considered a plausible therapeutic target, the crosstalk between genetic and metabolic alterations throughout cancer types is not clearly defined. In this review, we summarise the present understanding of the interactions between genetic drivers of cellular transformation and cancer-associated metabolic changes, and how these interactions contribute to metabolic heterogeneity of tumours. We discuss the essential question of whether changes in metabolism are a cause or a consequence in the formation of cancer. We highlight two modes of how metabolism contributes to tumour formation. One is when metabolic reprogramming occurs downstream of oncogenic mutations in signalling pathways and supports tumorigenesis. The other is where metabolic reprogramming initiates transformation being either downstream of mutations in oncometabolite genes or induced by chronic wounding, inflammation, oxygen stress or metabolic diseases. Finally, we focus on the factors that can contribute to metabolic heterogeneity in tumours, including genetic heterogeneity, immunomodulatory factors and tissue architecture. We believe that an in-depth understanding of cancer metabolic reprogramming, and the role of metabolic dysregulation in tumour initiation and progression, can help identify cellular vulnerabilities that can be exploited for therapeutic use.
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spelling pubmed-70519702020-07-01 Defining a metabolic landscape of tumours: genome meets metabolism Seth Nanda, Chandan Venkateswaran, Sharavan Vishaan Patani, Neill Yuneva, Mariia Br J Cancer Review Article Cancer is a complex disease of multiple alterations occuring at the epigenomic, genomic, transcriptomic, proteomic and/or metabolic levels. The contribution of genetic mutations in cancer initiation, progression and evolution is well understood. However, although metabolic changes in cancer have long been acknowledged and considered a plausible therapeutic target, the crosstalk between genetic and metabolic alterations throughout cancer types is not clearly defined. In this review, we summarise the present understanding of the interactions between genetic drivers of cellular transformation and cancer-associated metabolic changes, and how these interactions contribute to metabolic heterogeneity of tumours. We discuss the essential question of whether changes in metabolism are a cause or a consequence in the formation of cancer. We highlight two modes of how metabolism contributes to tumour formation. One is when metabolic reprogramming occurs downstream of oncogenic mutations in signalling pathways and supports tumorigenesis. The other is where metabolic reprogramming initiates transformation being either downstream of mutations in oncometabolite genes or induced by chronic wounding, inflammation, oxygen stress or metabolic diseases. Finally, we focus on the factors that can contribute to metabolic heterogeneity in tumours, including genetic heterogeneity, immunomodulatory factors and tissue architecture. We believe that an in-depth understanding of cancer metabolic reprogramming, and the role of metabolic dysregulation in tumour initiation and progression, can help identify cellular vulnerabilities that can be exploited for therapeutic use. Nature Publishing Group UK 2019-12-10 2020-01-21 /pmc/articles/PMC7051970/ /pubmed/31819196 http://dx.doi.org/10.1038/s41416-019-0663-7 Text en © The Author(s), under exclusive licence to Cancer Research UK 2019 https://creativecommons.org/licenses/by/4.0/Note: This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).
spellingShingle Review Article
Seth Nanda, Chandan
Venkateswaran, Sharavan Vishaan
Patani, Neill
Yuneva, Mariia
Defining a metabolic landscape of tumours: genome meets metabolism
title Defining a metabolic landscape of tumours: genome meets metabolism
title_full Defining a metabolic landscape of tumours: genome meets metabolism
title_fullStr Defining a metabolic landscape of tumours: genome meets metabolism
title_full_unstemmed Defining a metabolic landscape of tumours: genome meets metabolism
title_short Defining a metabolic landscape of tumours: genome meets metabolism
title_sort defining a metabolic landscape of tumours: genome meets metabolism
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051970/
https://www.ncbi.nlm.nih.gov/pubmed/31819196
http://dx.doi.org/10.1038/s41416-019-0663-7
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