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BMC Medicine
Published in: BMC Medicine 1/2017

Open Access 01-12-2017 | Review

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

Authors: Deborah R. Caswell, Charles Swanton

Published in: BMC Medicine | Issue 1/2017

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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.
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Metadata
Title
The role of tumour heterogeneity and clonal cooperativity in metastasis, immune evasion and clinical outcome
Authors
Deborah R. Caswell
Charles Swanton
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2017
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-017-0900-y

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