Abstract
This chapter examines the role of tumor stem cell dynamics on the evolution of drug resistant mutants in the context of CML therapy with small molecule inhibitors. In particular, the role of tumor stem cell quiescence is examined. Modeling shows that in the context of treatment with a single drug, parameters that determine the kinetics of cellular quiescence do not affect the probability of treatment failure as a result of drug resistant mutants. On the other hand, if two or more drugs are used in combination to treat the cancer, then treatment failure as a result of drug resistance is promoted by the occurrence of cellular quiescence. Interestingly, while cellular quiescence significantly prolongs the time until the cancer has dropped to low numbers or has been driven extinct, the model predicts that drug resistance does not evolve during this treatment phase. The occurrence of cellular quiescence increases the likelihood that resistant mutants are generated during the growth phase of the cancer before therapy is initiated.
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Notes
- 1.
In order to perform the Taylor series expansion we assume that \(u\ll 1-\alpha /L\); for \(\alpha \) very close to \(L\), the value \(1-\alpha /L\) would have to be taken to be the small parameter of expansion.
References
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Piotrowska, M. J., Enderling, H., van der Heiden, U., Mackey, M.C.: Mathematical Modeling of Stem Cells Related to Cancer, in Cancer and stem cells (eds. T. Dittmar & K.S. Zanker), Nova Science Publisher, Hauppauge, NY (2008)
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Komarova, N.L., Wodarz, D. (2014). Effect of Cellular Quiescence on the Evolution of Drug Resistance in CML. 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_6
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DOI: https://doi.org/10.1007/978-1-4614-8301-4_6
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