It is generally accepted that the initiation and progression of cancers is the result of somatic clonal evolution. Despite many peculiarities, evolution within populations of somatic cells should obey the same Darwinian principles as evolution within natural populations, i.e. variability of heritable phenotypes provides the substrate for context-specific selection forces leading to increased population frequencies of phenotypes, which are better adapted to their environment. Yet, within cancer biology, the more prevalent way to view evolution is as being entirely driven by the accumulation of "driver" mutations. Context-specific selection forces are either ignored, or viewed as constraints from which tumor cells liberate themselves during the course of malignant progression. In this review, we will argue that explicitly focusing on selection forces acting on the populations of neoplastic cells as the driving force of somatic clonal evolution might provide for a more accurate conceptual framework compared to the mutation-centric driver gene paradigm. Whereas little can be done to counteract the "bad luck" of stochastic occurrences of cancer-related mutations, changes in selective pressures and the phenotypic adaptations they induce can, in principle, be exploited to limit the incidence of cancers and to increase the efficiency of existing and future therapies. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby.

中文翻译：

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体细胞克隆进化：以选择为中心的观点。

人们普遍认为，癌症的发生和发展是体细胞克隆进化的结果。尽管有许多特殊性，体细胞群体内的进化应遵循与自然群体内进化相同的达尔文原理，即，遗传表型的可变性为特定背景的选择力提供了基础，从而导致表型群体频率的增加，从而更好地适应了它们的表型。环境。然而，在癌症生物学中，更普遍的观察进化的方式是完全由“驱动”突变的积累所驱动。特定于上下文的选择力要么被忽略，要么被视为在恶性进展过程中肿瘤细胞从中释放出来的限制。在这篇评论中，我们将论证，与以突变为中心的驱动基因范式相比，明确关注作用于肿瘤细胞群体的选择力作为体细胞克隆进化的驱动力可能会提供更准确的概念框架。尽管几乎没有什么办法可以抵消与癌症相关的突变的随机发生的“厄运”，但原则上可以利用选择性压力的变化和它们诱导的表型适应来限制癌症的发生并提高癌症的发生率。现有和将来的疗法。本文是由Robert A. Gatenby博士编辑的题为：进化原理-癌症的异质性？的特刊的一部分。