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Optimizing Combination Therapies with Existing and Future CML Drugs

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  • Allen A Katouli
  • Natalia L Komarova

Abstract

Small-molecule inhibitors imatinib, dasatinib and nilotinib have been developed to treat Chromic Myeloid Leukemia (CML). The existence of a triple-cross-resistant mutation, T315I, has been a challenging problem, which can be overcome by finding new inhibitors. Many new compounds active against T315I mutants are now at different stages of development. In this paper we develop an algorithm which can weigh different combination treatment protocols according to their cross-resistance properties, and find the protocols with the highest probability of treatment success. This algorithm also takes into account drug toxicity by minimizing the number of drugs used, and their concentration. Although our methodology is based on a stochastic model of CML microevolution, the algorithm itself does not require measurements of any parameters (such as mutation rates, or division/death rates of cells), and can be used by medical professionals without a mathematical background. For illustration, we apply this algorithm to the mutation data obtained in [1], [2].

Suggested Citation

  • Allen A Katouli & Natalia L Komarova, 2010. "Optimizing Combination Therapies with Existing and Future CML Drugs," PLOS ONE, Public Library of Science, vol. 5(8), pages 1-12, August.
    • Handle: RePEc:plo:pone00:0012300
    DOI: 10.1371/journal.pone.0012300
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    Cited by:

    1. Benjamin Werner & David Lutz & Tim H Brümmendorf & Arne Traulsen & Stefan Balabanov, 2011. "Dynamics of Resistance Development to Imatinib under Increasing Selection Pressure: A Combination of Mathematical Models and In Vitro Data," PLOS ONE, Public Library of Science, vol. 6(12), pages 1-8, December.

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