Cancer phenotype and evolutionary games 1/17 Cancer phenotype as the outcome of an evolutionary game between normal and malignant cells

There is variability in the cancer phenotype across individuals: Two patients with the same tumor may experience different disease life histories, resulting from genetic variation within the tumor and from the interaction between the tumor and the host. Up to now, phenotypic variability has precluded a clear-cut identification of the fundamental characteristics of a given tumor type. Here we show how a game theoretical approach allows their identification and provides a natural explanation for phenotypic variability. Tumor dynamics is determined by the frequency dependent fitness of different cell populations, resulting from the benefits and costs accrued by each cell type in the presence of others. We study multiple myeloma (MM), a neoplastic disorder resulting from the expansion of plasma cells that ‘typically’ leads to anemia and bone destruction. We show how complex biochemical signals translate into cell fitness and determine disease dynamics. The present paradigm is general and extends well beyond MM, and even to non neoplastic disorders. Furthermore, it provides a new perspective in dealing with cancer eradication: Instead of trying to kill all cancer cells, therapies should aim at reducing the fitness of malignant cells compared to normal cells, allowing natural selection to eradicate the tumor. Cancer phenotype and evolutionary games 2/17