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.

中文翻译：

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癌症进化：达尔文及以后


近几十年来的临床和实验室研究已经确定分支进化是癌症的一个特征。然而，虽然以体细胞选择为基础，但一些证据表明，仅达尔文模型不足以完全解释癌症进化。首先，宏观进化事件在肿瘤发生和进展中的作用与达尔文渐进主义的中心论点相矛盾。全基因组加倍、染色体染色体复合和染色体碎裂代表了可驱动肿瘤进化的单一灾难性事件的例子。其次，中性进化可以在某些肿瘤中发挥作用，这表明选择并不总是驱动进化。第三，对衰老体细胞作用的日益认识导致了最近年龄依赖性致癌的广义理论。在这里，我们回顾这些概念和其他概念，它们共同主张超越达尔文的癌症进化模型。我们还强调了可以通过针对非达尔文进化模式产生的癌症脆弱性来抓住的临床机会。