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Tumor diversity and the trade-off between universal cancer tasks

Published version
Peer-reviewed

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Authors

Szekely, Pablo 
Bar, Noam 
Zimmer, Anat 
Sheftel, Hila 

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.

Description

Funder: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation); doi: https://doi.org/10.13039/501100001711


Funder: Abisch-Frenkel-Stiftung (Abisch-Frenkel Foundation); doi: https://doi.org/10.13039/501100007362

Keywords

Article, /631/67, /631/553, /38/23, /38/39, /45/47, article

Journal Title

Nature Communications

Conference Name

Journal ISSN

2041-1723

Volume Title

10

Publisher

Nature Publishing Group UK