Combination therapies and intra-tumoral competition: Insights from mathematical modeling.

Drug resistance is one of the major obstacles to a successful treatment of cancer and, in turn, has been recognized to be linked to intratumoral heterogeneity, which increases the probability of the emergence of cancer clones refractory to treatment. Combination therapies have been introduced to overcome resistance, but the design of successful combined protocols is still an open problem. In order to provide some indications on the effectiveness of medical treatments, a mathematical model is proposed, comprising two cancer populations competing for resources and with different susceptibilities to the action of immune system cells and therapies: the focus is on the effects of chemotherapy and immunotherapy, used singularly or in combination. First, numerical predictions of the model have been tested with experimental data from the literature and next therapeutic protocols with different doses and temporal order have been simulated. Finally the role of competitive interactions has been also investigated, to provide some insights on the role of competitive interactions among cancer clones in determining treatment outcomes.