Darwinian Dynamics of Intratumoral Heterogeneity: Not Solely Random Mutations but Also Variable Environmental Selection Forces.

ABSTRACT: Spatial heterogeneity in tumors is generally thought to result from branching clonal evolution driven by random mutations that accumulate during tumor development. However, this concept rests on the implicit assumption that cancer cells never evolve to a fitness maximum because they can always acquire mutations that increase proliferative capacity. In this study, we investigated the validity of this assumption. Using evolutionary game theory, we demonstrate that local cancer cell populations will rapidly converge to the fittest phenotype given a stable environment. In such settings, cellular spatial heterogeneity in a tumor will be largely governed by regional variations in environmental conditions, for example, alterations in blood flow. Model simulations specifically predict a common spa

SUBMITTER: Lloyd MC 

PROVIDER: S-EPMC5384728 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature