Time-dependent synergy for multi-agent anticancer therapy

A synergy between two therapeutic agents occurs when the effect of using both is greater than the sum of the effects of using each of them separately. There are several methods of detecting synergies in the literature, but they do not take into account the relationship between the times in which the factors act. In the article, we propose and justify the use of second-order sensitivity analysis as a potential tool for the detection and visualization of this type of synergy. We test and illustrate the proposed approach using four exemplary models of combined radio-chemotherapy of cancer.