Journal
BMC MEDICINE
Volume 15, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12916-017-0900-y
Keywords
Intratumour heterogeneity; Tumour progression; Metastasis; Linear evolution; Branched evolution; Competitive evolution; Cooperative evolution; Mutation burden; Immunotherapy; Aneuploidy tolerance
Categories
Funding
- Francis Crick Institute from Cancer Research UK [FC001169]
- UK Medical Research Council [MR/FC001169/1]
- Wellcome Trust [FC001169]
- Cancer Research UK (TRACERx)
- CRUK Lung Cancer Centre of Excellence
- Stand Up 2 Cancer (SU2C)
- Rosetrees Trust
- NovoNordisk Foundation [16584]
- Prostate Cancer Foundation
- Breast Cancer Research Foundation (BCRF)
- European Research Council (THESEUS)
- Marie Curie Network PloidyNet
- National Institute for Health Research
- University College London Hospitals Biomedical Research Centre
- Cancer Research UK University College London Experimental Cancer Medicine Centre
- MRC [MR/P014712/1] Funding Source: UKRI
- Cancer Research UK [20466, 19310, 17786] Funding Source: researchfish
- Medical Research Council [MR/P014712/1] Funding Source: researchfish
- Novo Nordisk Fonden [NNF15OC0016584] Funding Source: researchfish
- Rosetrees Trust [M179, M445, M391, M640, M231-CD1] Funding Source: researchfish
- The Francis Crick Institute [10172, VEG 108844, A1278, 10485, 10169, 10359, 10467, C28575/A25223, 10170, 10174, C60895/A23896] Funding Source: researchfish
Ask authors/readers for more resources
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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