Tumour heterogeneity and the evolutionary trade-offs of cancer

被引:116
作者
Hausser, Jean [1 ,2 ]
Alon, Uri [3 ]
机构
[1] Karolinska Inst, Dept Cellular & Mol Biol, Solna, Sweden
[2] SciLifeLab, Solna, Sweden
[3] Weizmann Inst Sci, Dept Mol & Cell Biol, Rehovot, Israel
基金
瑞士国家科学基金会; 瑞典研究理事会;
关键词
GENE-EXPRESSION; SPATIAL RECONSTRUCTION; REDUCED PROLIFERATION; CLONAL EVOLUTION; DRUG-RESISTANCE; MICROENVIRONMENT; PROGRESSION; GEOMETRY; DYNAMICS; TUMORIGENESIS;
D O I
10.1038/s41568-020-0241-6
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
This Perspective discusses the theory of multi-task evolution in cancer, which can contribute to understanding tumour diversity. It introduces the concept of generalist and specialist tumours in the contexts of driver mutations and discusses the potential applications to interpret intratumour heterogeneity. Tumours vary in gene expression programmes and genetic alterations. Understanding this diversity and its biological meaning requires a theoretical framework, which could in turn guide the development of more accurate prognosis and therapy. Here, we review the theory of multi-task evolution of cancer, which is based upon the premise that tumours evolve in the host and face selection trade-offs between multiple biological functions. This theory can help identify the major biological tasks that cancer cells perform and the trade-offs between these tasks. It introduces the concept of specialist tumours, which focus on one task, and generalist tumours, which perform several tasks. Specialist tumours are suggested to be sensitive to therapy targeting their main task. Driver mutations tune gene expression towards specific tasks in a tissue-dependent manner and thus help to determine whether a tumour is specialist or generalist. We discuss potential applications of the theory of multi-task evolution to interpret the spatial organization of tumours and intratumour heterogeneity.
引用
收藏
页码:247 / 257
页数:11
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