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

André Rocha; Claudia Manini; José I López; Annick Laruelle

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arXiv · 2510.23360

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

André Rocha·Claudia Manini·José I López·Annick Laruelle

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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.

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André Rocha, Claudia Manini, José I López, Annick Laruelle. 2025-10-27. Effect of intratumor heterogeneity in managing the go-or-grow dichotomy of cancer cells: a game theory modeling to understand metastasis. https://arxiv.org/abs/2510.23360

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