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