Optimal Therapy Scheduling Based on a Pair of Collaterally Sensitive Drugs

Bulletin of Mathematical Biology
Nara YoonJacob G Scott


Despite major strides in the treatment of cancer, the development of drug resistance remains a major hurdle. One strategy which has been proposed to address this is the sequential application of drug therapies where resistance to one drug induces sensitivity to another drug, a concept called collateral sensitivity. The optimal timing of drug switching in these situations, however, remains unknown. To study this, we developed a dynamical model of sequential therapy on heterogeneous tumors comprised of resistant and sensitive cells. A pair of drugs (DrugA, DrugB) are utilized and are periodically switched during therapy. Assuming resistant cells to one drug are collaterally sensitive to the opposing drug, we classified cancer cells into two groups, [Formula: see text] and [Formula: see text], each of which is a subpopulation of cells resistant to the indicated drug and concurrently sensitive to the other, and we subsequently explored the resulting population dynamics. Specifically, based on a system of ordinary differential equations for [Formula: see text] and [Formula: see text], we determined that the optimal treatment strategy consists of two stages: an initial stage in which a chosen effective drug is utilized until a specif...Continue Reading


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