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Cancer evolution: Darwin and beyond

Vendramin, R; Litchfield, K; Swanton, C; (2021) Cancer evolution: Darwin and beyond. EMBO Journal , Article e108389. 10.15252/embj.2021108389. Green open access

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Abstract

Clinical and laboratory studies over recent decades have established branched evolution as a feature of cancer. However, while grounded in somatic selection, several lines of evidence suggest a Darwinian model alone is insufficient to fully explain cancer evolution. First, the role of macroevolutionary events in tumour initiation and progression contradicts Darwin's central thesis of gradualism. Whole-genome doubling, chromosomal chromoplexy and chromothripsis represent examples of single catastrophic events which can drive tumour evolution. Second, neutral evolution can play a role in some tumours, indicating that selection is not always driving evolution. Third, increasing appreciation of the role of the ageing soma has led to recent generalised theories of age-dependent carcinogenesis. Here, we review these concepts and others, which collectively argue for a model of cancer evolution which extends beyond Darwin. We also highlight clinical opportunities which can be grasped through targeting cancer vulnerabilities arising from non-Darwinian patterns of evolution.

Type: Article
Title: Cancer evolution: Darwin and beyond
Open access status: An open access version is available from UCL Discovery
DOI: 10.15252/embj.2021108389
Publisher version: http://dx.doi.org/10.15252/embj.2021108389
Language: English
Additional information: © 2021 The Authors. Published under the terms of the CC BY 4.0 license
Keywords: cancer evolution, cancer therapy, tumour heterogeneity, CIRCULATING TUMOR DNA, CLONAL EVOLUTION, INTRATUMOR HETEROGENEITY, LUNG-CANCER, CHROMOSOMAL INSTABILITY, ACQUIRED-RESISTANCE, TARGETED THERAPY, COLLATERAL SENSITIVITY, GENOMIC INSTABILITY, RESIDUAL DISEASE
UCL classification: UCL
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: https://discovery.ucl.ac.uk/id/eprint/10134162
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