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The role of tumour heterogeneity and clonal cooperativity in metastasis, immune evasion and clinical outcome

Caswell, DR; Swanton, C; (2017) The role of tumour heterogeneity and clonal cooperativity in metastasis, immune evasion and clinical outcome. [Review]. BMC Medicine , 15 , Article 133. 10.1186/s12916-017-0900-y. Green open access

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Abstract

Background: The advent of rapid and inexpensive sequencing technology allows scientists to decipher heterogeneity within primary tumours, between primary and metastatic sites, and between metastases. Charting the evolutionary history of individual tumours has revealed drivers of tumour heterogeneity and highlighted its impact on therapeutic outcomes. Discussion: Scientists are using improved sequencing technologies to characterise and address the challenge of tumour heterogeneity, which is a major cause of resistance to therapy and relapse. Heterogeneity may fuel metastasis through the selection of rare, aggressive, somatically altered cells. However, extreme levels of chromosomal instability, which contribute to intratumour heterogeneity, are associated with improved patient outcomes, suggesting a delicate balance between high and low levels of genome instability. Conclusions: We review evidence that intratumour heterogeneity influences tumour evolution, including metastasis, drug resistance, and the immune response. We discuss the prevalence of tumour heterogeneity, and how it can be initiated and sustained by external and internal forces. Understanding tumour evolution and metastasis could yield novel therapies that leverage the immune system to control emerging tumour neo-antigens.

Type: Article
Title: The role of tumour heterogeneity and clonal cooperativity in metastasis, immune evasion and clinical outcome
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s12916-017-0900-y
Publisher version: http://doi.org/10.1186/s12916-017-0900-y
Language: English
Additional information: Copyright © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: Intratumour heterogeneity, Tumour progression, Metastasis, Linear evolution, Branched evolution, Competitive evolution, Cooperative evolution, Mutation burden, Immunotherapy, Aneuploidy tolerance
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: http://discovery.ucl.ac.uk/id/eprint/10050887
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