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

Evolution of acquired resistance to anti-cancer therapy

Jasmine Foo  1 , Franziska Michor  2
Affiliations
Review

Evolution of acquired resistance to anti-cancer therapy

Jasmine Foo et al. J Theor Biol. .

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.

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Figures

Figure 1
Figure 1
Evolutionary modeling has contributed to elucidating the risk of pre-existing resistance, the probability that resistance arises during treatment, the effects of the choice of dosing strategies on the dynamics of resistant cells, and the optimal strategy to prevent or delay the onset of drug resistance. For details on the references, please see the list of citations.
Figure 2
Figure 2
Progress towards an understanding of the evolutionary dynamics of acquired resistance requires close collaboration between researchers performing mathematical modeling studies as well as cell line and mouse model experiments and clinical investigations.
See this image and copyright information in PMC

References

    1. Goodman LS, Wintrobe MX, Damshek W, Goodman MJ. Nitrogen Mustard Therapy. J Am Med Assoc. 1946;132:126–132. - PubMed
    1. Gilman A. The initial clinical trial of nitrogen mustard. Am J Surg. 1963;105:574–578. - PubMed
    1. Farber SDL, Mercer RD, Sylvester RF, Wolff JA. Temporary remissions in acute leukemia in children produced by folic antagonist, 4-aminopteroylglutamic acid (aminopterin) N Eng J Med. 1948;238:787–793. - PubMed
    1. Li MCHR, Bergenstal DM. Therapy of choriocarcinoma and related trophoblastic tumors with folic acid and purine antagonists. N Eng J Med. 1958;259:66–74. - PubMed
    1. Sawyers C. Targeted cancer therapy. Nature. 2004;432:294–297. - PubMed

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