Tumor diversity and the trade-off between universal cancer tasks

Nat Commun. 2019 Nov 28;10(1):5423. doi: 10.1038/s41467-019-13195-1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division / genetics*
  • Energy Metabolism / genetics*
  • Gene Expression
  • Humans
  • Lipogenesis / genetics*
  • Mutation
  • Neoplasm Invasiveness / genetics*
  • Neoplasms / genetics*
  • Systems Biology
  • Tumor Escape / genetics*