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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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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. |
format | Online Article Text |
id | pubmed-7051970 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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