Effect of intratumor heterogeneity in managing the go-or-grow dichotomy of cancer cells: a game theory modeling to understand metastasis

TL;DR

This paper uses game theory modeling to explore how intratumor heterogeneity influences cancer cell decisions to stay or metastasize, aligning with empirical observations in renal cell carcinomas.

Contribution

It introduces a static evolutionary game model to explain the coexistence of primary and metastatic tumors and the conditions promoting metastasis, providing mathematical support for observed cancer behaviors.

Findings

Model predicts coexistence of primary and metastatic tumors.

Metastatic likelihood increases with certain genetic mutations.

Results align with empirical data in renal cell carcinomas.

Abstract

We study the effect of intratumor heterogeneity in the likelihood of cancer cells moving from a primary tumor to other sites in the human body, generating a metastatic process. We model different scenarios of competition between tumor cells using a static evolutionary game in which cells compete for nutrients and oxygen and might choose to stay and proliferate in the primary tumor or opt to a motility strategy in order to find resources in a metastatic site. The theoretical results found in the evolutionarily equilibrium in the mathematical model are in line with the empirical results observed in oncology, namely, the coexistence of both primary and metastatic tumors and the conditions that favor a metastatic process. Particularly, the model finds mathematical support for what is empirically observed in punctuated and branching cancers for the specific case of clear cell renal cell carcinomas: motility of cells is larger in punctuated cancers if the proportion of BAP1 mutations remain below a given cell proportion threshold.