文章：

癌症是一个进化和生态过程

Cancer as an evolutionary and ecological process

原文发布日期：2006-11-16

DOI: 10.1038/nrc2013

类型: Review Article

开放获取: 否

要点：

1. Neoplasms are composed of an ecosystem of evolving clones, competing and cooperating with each other and other cells in their microenvironment, and this has important implications for both neoplastic progression and therapy.
2. Selection at the different levels of genes, cells and organisms might conflict, and have resulted in a legacy of tumour-suppression mechanisms and vulnerability to oncogenesis in our genomes.
3. Most of the dynamics of evolution have not been measured in neoplasms, including mutation rates, fitness effects of mutations, generation times, population structure, the frequency of selective sweeps and the selective effects of our therapies.
4. Many of the genetic and epigenetic alterations observed in neoplasms are evolutionarily neutral.
5. Cancer therapies select for cancer stem cells with resistance mutations, although various evolutionary approaches have been suggested to overcome this problem, including selecting for benign or chemosensitive cells, altering the carrying capacity of the neoplasm and the competitive effects of neoplastic and normal cells on each other.
6. Dispersal theory suggests that high cell mortality and variation of resources and population densities across space might select for metastasis.
7. There is evidence of competition, predation, parasitism and mutualism between co-evolving clones in and around a neoplasm.
8. We will need to interfere with clonal evolution and alter the fitness landscapes of neoplastic cells to prevent or cure cancer. Evolutionary biology should be central to this endeavor.

要点翻译：

1. 肿瘤由不断演化的克隆群体构成的生态系统组成，这些克隆彼此之间以及与其微环境中的其他细胞相互竞争与合作，这对肿瘤进展和治疗具有重要意义。
2. 基因、细胞和生物体不同层级的选择可能存在冲突，并在我们基因组中留下了肿瘤抑制机制的痕迹及对肿瘤发生的易感性。
3. 目前尚未对肿瘤演化过程中的多数动态参数进行量化，包括突变率、突变的适应效应、代际时间、种群结构、选择性清除频率以及治疗的选择作用。
4. 在肿瘤中观察到的大多数遗传和表观遗传改变在进化上是中性的。
5. 癌症疗法会筛选出携带耐药突变的癌症干细胞，尽管已有多种进化策略被提出以解决该问题，包括筛选良性或化疗敏感细胞、改变肿瘤承载能力以及调整肿瘤细胞与正常细胞间的竞争效应。
6. 扩散理论表明，高细胞死亡率以及资源与种群密度的空间异质性可能促进转移表型的筛选。
7. 有证据显示共同演化的克隆在肿瘤内部及周围存在竞争、捕食、寄生和互利共生关系。
8. 我们需要干预克隆演化并改变肿瘤细胞的适应度景观，才能预防或治愈癌症。进化生物学应成为这一努力的核心支柱。

英文摘要：

Neoplasms are microcosms of evolution. Within a neoplasm, a mosaic of mutant cells compete for space and resources, evade predation by the immune system and can even cooperate to disperse and colonize new organs. The evolution of neoplastic cells explains both why we get cancer and why it has been so difficult to cure. The tools of evolutionary biology and ecology are providing new insights into neoplastic progression and the clinical control of cancer.

摘要翻译： 

肿瘤是进化的缩影。在肿瘤内部，突变细胞的镶嵌体为争夺空间和资源而竞争，逃避免疫系统的捕食，甚至还能合作扩散并殖民新的器官。肿瘤细胞的进化既解释了我们为何会患癌，也说明了为何癌症如此难以治愈。进化生物学和生态学的工具正在为肿瘤进展及癌症的临床控制提供新的洞见。

原文链接：

Cancer as an evolutionary and ecological process