Using game theory to analyse the metastasis process

Game theory is a general theory that studies strategic situations in which actors or players choose different actions designed to maximise 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 behaviour 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 tumour cells themselves, and secondly between tumour cells and host cells, which are not fully understood and remain one of the main frontiers in oncology.

Modern molecular technologies are progressively unravelling 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 tumour. By means of modelling, 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 tumours is like," Laruelle explained.

Cell diversity in a tumour could harm tumour cells

In this respect, they have analysed 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 tumour cells which would involve seeking collective stability away from the primary tumour in order to improve their collective well-being and avoid extinction. The spatial specialisation of tumours with metastatic subclones located inside the tumour, the demonstrated capability of metastases to metastasise and the sociological interactions of tumour cells revealed by game theory support the argument of this perspective in the sense that the search for a better environment by tumour cells occurs constantly in malignant tumours.

"The surmise that game theory has revealed for us is that greater cell heterogeneity in tumours might be bad for the cancer cells, but better for the patient. It seems that a cancer that has high cell diversity is more favourable for the patient than a cancer in which the tumour is not very diverse at all," she said. This shows "that in the long term eliminating all types of cells in a tumour 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.”

Additional information

The study is the outcome of the collaboration between the Ikerbasque professor Annick Laruelle (of the UPV/EHU's Department of Economic Analysis), Claudia Manini (of the Department of Pathology at the San Giovanni Bosco Hospital in Turin), Elena Iñarra (of the UPV/EHU's Institute of Public Economics) and José I. López (of the Pathology Department at Cruces University Hospital and Biocruces).

Game theory is a general theory that studies strategic situations in which actors or players choose different actions designed to maximise 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 behaviour 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 tumour cells themselves, and secondly between tumour cells and host cells, which are not fully understood and remain one of the main frontiers in oncology.

Modern molecular technologies are progressively unravelling 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 tumour. By means of modelling, 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 tumours is like," Laruelle explained.

Cell diversity in a tumour could harm tumour cells

In this respect, they have analysed 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 tumour cells which would involve seeking collective stability away from the primary tumour in order to improve their collective well-being and avoid extinction. The spatial specialisation of tumours with metastatic subclones located inside the tumour, the demonstrated capability of metastases to metastasise and the sociological interactions of tumour cells revealed by game theory support the argument of this perspective in the sense that the search for a better environment by tumour cells occurs constantly in malignant tumours.

"The surmise that game theory has revealed for us is that greater cell heterogeneity in tumours might be bad for the cancer cells, but better for the patient. It seems that a cancer that has high cell diversity is more favourable for the patient than a cancer in which the tumour is not very diverse at all," she said. This shows "that in the long term eliminating all types of cells in a tumour 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.”

Additional information

The study is the outcome of the collaboration between the Ikerbasque professor Annick Laruelle (of the UPV/EHU's Department of Economic Analysis), Claudia Manini (of the Department of Pathology at the San Giovanni Bosco Hospital in Turin), Elena Iñarra (of the UPV/EHU's Institute of Public Economics) and José I. López (of the Pathology Department at Cruces University Hospital and Biocruces).