Development of anti-cancer drug medication scheduling method based on the systematic understanding of biochemical networks

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By using a circadian rhythm-cell cycle model, we identified differences in cell cycles between normal and cancer cells, and proposed an efficient drug administration strategy. In order to construct simulation models, the values of kinetic parameters need to be estimated so that the models fit to experimental data. Generally, the parameter values measured in vitro are different from those in vivo. However, the in vitro measurements can be clues to in vivo values. In this study, we developed a novel parameter estimation method that uses in vitro measurements. We revealed and mathematically proved that the long negative feedback loops make oscillations robust to fluctuations in kinetic parameters.