Exploiting Evolution to Treat Drug Resistance: Combination Therapy and the Double Bind

Mol Pharm. 2012 Apr 2;9(4):914-21. doi: 10.1021/mp200458e. Epub 2012 Mar 19.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Drug Resistance, Neoplasm*
  • Humans
  • Immunotherapy
  • Models, Theoretical
  • Neoplasms / drug therapy
  • Neoplasms / therapy