Optimal intervention strategies for cyclic therapeutic methods.

External control of a genetic regulatory network is used for the purpose of avoiding undesirable states such as those associated with a disease. Certain types of cancer therapies, such as chemotherapy, are given in cycles with each treatment being followed by a recovery period. During the recovery period, the side effects tend to gradually subside. In this paper, it is shown how an optimal cyclic intervention strategy can be devised for any Markovian genetic regulatory network. The effectiveness of optimal cyclic therapies is demonstrated through numerical studies for random networks. Furthermore, an optimal cyclic policy is derived to control the behavior of a regulatory model of the mammalian cell-cycle network.