Evolution of acquired resistance to anti-cancer therapy

J Theor Biol. 2014 Aug 21:355:10-20. doi: 10.1016/j.jtbi.2014.02.025. Epub 2014 Mar 25.

Abstract

Acquired drug resistance is a major limitation for the successful treatment of cancer. Resistance can emerge due to a variety of reasons including host environmental factors as well as genetic or epigenetic alterations in the cancer cells. Evolutionary theory has contributed to the understanding of the dynamics of resistance mutations in a cancer cell population, the risk of resistance pre-existing before the initiation of therapy, the composition of drug cocktails necessary to prevent the emergence of resistance, and optimum drug administration schedules for patient populations at risk of evolving acquired resistance. Here we review recent advances towards elucidating the evolutionary dynamics of acquired drug resistance and outline how evolutionary thinking can contribute to outstanding questions in the field.

Keywords: Cancer; Drug resistance; Evolution; Mathematical modeling; Optimal dosing strategies.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Drug Resistance, Neoplasm*
  • Evolution, Molecular*
  • Humans
  • Models, Biological*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism*
  • Neoplasms / pathology

Substances

  • Antineoplastic Agents