Tumor diversity and the trade-off between universal cancer tasks

Jean Hausser, Pablo Szekely, Noam Bar, Anat Zimmer, Hila Sheftel, Carlos Caldas () and Uri Alon ()
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Jean Hausser: Weizmann Institute of Science
Pablo Szekely: Weizmann Institute of Science
Noam Bar: Weizmann Institute of Science
Anat Zimmer: Weizmann Institute of Science
Hila Sheftel: Weizmann Institute of Science
Carlos Caldas: University of Cambridge
Uri Alon: Weizmann Institute of Science

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract Recent advances have enabled powerful methods to sort tumors into prognosis and treatment groups. We are still missing, however, a general theoretical framework to understand the vast diversity of tumor gene expression and mutations. Here we present a framework based on multi-task evolution theory, using the fact that tumors need to perform multiple tasks that contribute to their fitness. We find that trade-offs between tasks constrain tumor gene-expression to a continuum bounded by a polyhedron whose vertices are gene-expression profiles, each specializing in one task. We find five universal cancer tasks across tissue-types: cell-division, biomass and energy, lipogenesis, immune-interaction and invasion and tissue-remodeling. Tumors that specialize in a task are sensitive to drugs that interfere with this task. Driver, but not passenger, mutations tune gene-expression towards specialization in specific tasks. This approach can integrate additional types of molecular data into a framework of tumor diversity grounded in evolutionary theory.

Date: 2019
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DOI: 10.1038/s41467-019-13195-1

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