Journal
MOLECULAR PHARMACEUTICS
Volume 9, Issue 4, Pages 914-921Publisher
AMER CHEMICAL SOC
DOI: 10.1021/mp200458e
Keywords
evolutionary game theory; evolutionary double bind; mathematical modeling; immunotherapy; chemotherapy; combination therapy; comensalism
Funding
- NCI [1U01CA151924-01A1]
- ICBP [5U54 CA113007]
- PSOC [U54 CA143970-01]
- TMEN [1U54 CA126505]
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Although many anticancer therapies are successful in killing a large percentage of tumor cells when initially administered, the evolutionary dynamics underpinning tumor progression mean that, often, resistance is an inevitable outcome. Research in the field of ecology suggests that an evolutionary double bind could be an effective way to treat tumors. In an evolutionary double bind two therapies are used in combination such that evolving resistance to one leaves individuals more susceptible to the other. In this paper we present a general evolutionary game theory framework of a double bind to study the effect that such an approach would have in cancer. Furthermore we use this mathematical framework to understand recent experimental results that suggest a synergistic effect between a p53 cancer vaccine and chemotherapy. Our model recapitulates the latest experimental data and provides an explanation for its effectiveness based on the commensalistic relationship between the tumor phenotypes.
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