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Cross Resistance: Treatment and Modeling

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Targeted Cancer Treatment in Silico

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Abstract

We have so far considered combination therapy under the assumption that resistance against one drug does not confer resistance to any of the other drugs in use. While this applies to many of the point mutations that induce resistance against imatinib, dastinib, and nilotinib, one mutation, T315I, confers resistance to all three drugs, i.e., there is complete cross-resistance. This chapter examines the effectiveness of combination therapy in the presence of the cross-resistant T315I mutation. The combination of two drugs is found to increase the probability of treatment success despite this cross-resistance. Combining more than two drugs, however, does not provide further advantages. Hence, according to the model, only the two most effective drugs should be used in combination for the prevention of drug resistance. We also discuss possible combinations involving inhibitors under development that aim to overcome the T315I mutation.

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Authors and Affiliations

  1. Department of Mathematics, University of California, Irvine, CA, 92697, USA

    Natalia L. Komarova

  2. Department of Ecology and Evolutionary Biology, University of California, Irvine, CA, 92697, USA

    Dominik Wodarz

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  1. Natalia L. Komarova
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  2. Dominik Wodarz
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Correspondence to Natalia L. Komarova .

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Komarova, N.L., Wodarz, D. (2014). Cross Resistance: Treatment and Modeling. In: Targeted Cancer Treatment in Silico. Modeling and Simulation in Science, Engineering and Technology. Birkhäuser, New York, NY. https://doi.org/10.1007/978-1-4614-8301-4_8

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