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Nat Rev Cancer. 2020 Apr;20(4):247-257. doi: 10.1038/s41568-020-0241-6. Epub 2020 Feb 24.

Tumour heterogeneity and the evolutionary trade-offs of cancer.

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Department of Cellular and Molecular Biology, Karolinska Institutet, Solna, Sweden.
SciLifeLab, Solna, Sweden.
Department of Molecular and Cell Biology, Weizmann Institute of Science, Rehovot, Israel.


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.


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