Game theory applied to cell encounters inside a tumor provides a sociological perspective on the possible behaviors of cells in a collectivity, and offers a more comprehensive understanding of the complex rules that govern a neoplasm. In the first step of a study that is still in progress, it has been surmised that metastasis occurs in response to tumor heterogeneity.
Game theory is a general theory that studies strategic situations in which actors or players choose different actions designed to maximize their benefits. It is therefore applicable to the evolution of species and can explain certain patterns that are difficult to understand. According to the approach of this theory, a game is a conflict situation in which the conflicting interests of individuals prevail, and in that context when one party makes a decision, the decision that the other party will make is influenced; so the outcome of the conflict is determined on the basis of all the decisions made by all the players.
Ikerbasque professor Annick Laruelle, an expert in game theory in the UPV/EHU's Department of Economic Analysis, explains that this theory, which was originally developed as a tool for understanding the behavior of the economy, "is currently used in a broad range of fields, and has also begun to be applied to the study of cancer, as it allows the dynamics of the processes to be better understood". A group made up of researchers from the UPV/EHU and pathologists from Biocruces and the San Giovanni Bosco Hospital in Turin (Italy) has launched a study to unveil the intricate interactions firstly between the tumor cells themselves, and secondly between tumor cells and host cells, which are not fully understood and remain one of the main frontiers in oncology.
Modern molecular technologies are progressively unraveling the genetic and epigenetic complexity of cancer, but many key questions remain unknown. Regarding cancer as a social dysfunction in a community of individuals has provided new perspectives of analysis with promising results.
What game theory is seeking are stable outcomes in the short or long term. In this first step, we have tried to understand the effect of cell heterogeneity in a tumor. By means of modeling, we can study how the resources between cells are distributed; in other words, we can propose models to try to see what the competition between cells in tumors is like."
Annick Laruelle, UPV/EHU's Department of Economic Analysis
Cell diversity in a tumor could harm tumor cells
In this respect, they have analyzed cell-cell interactions using a game-theory approach and have put forward the hypothesis that metastasis may simply be a specific response of a subset of tumor cells which would involve seeking collective stability away from the primary tumor in order to improve their collective well-being and avoid extinction. The spatial specialization of tumors with metastatic subclones located inside the tumor, the demonstrated capability of metastases to metastasize and the sociological interactions of tumor cells revealed by game theory support the argument of this perspective in the sense that the search for a better environment by tumor cells occurs constantly in malignant tumors.
"The surmise that game theory has revealed for us is that greater cell heterogeneity in tumors might be bad for the cancer cells, but better for the patient. It seems that a cancer that has high cell diversity is more favorable for the patient than a cancer in which the tumor is not very diverse at all," she said. This shows "that in the long term eliminating all types of cells in a tumor may not necessarily be a good thing, because there are cells that become resistant", she added.
However, Laruelle says that this is only the starting point of an ongoing piece of research, as game theory has corroborated situations seen in reality. In addition, the researcher stresses the importance of collaboration between people from very different fields: "It's very complicated because we speak different languages, but at the same time it's very interesting, very enriching.”
Laruelle, A., et al. (2021) Metastasis, an Example of Evolvability, Cancers. doi.org/10.3390/cancers13153653.