Abstract
Treatment with tyrosine kinase inhibitors, such as imatinib, have led to impressive therapy responses in the clinic. This chapter will discuss the pattern of decline of the BCR-ABL transcript numbers during treatment, and explore different hypotheses to explain them. Treatment typically results in a bi-phasic decline of BCR-ABL transcript numbers, where a faster phase of decline is followed by a slower phase. The earliest hypotheses tried to explain this pattern by assuming that more differentiated tumor cells are susceptible to the drug, while tumor stem cells are resistant. Subsequent work showed that the bi-phasic decline, and other, less common decline patterns found among patients, can be explained by differential susceptibility to the drug by activated and quiescent tumor stem cells. In addition to the basic tumor cell dynamics, mathematical models have also indicated that a transient rise of anti-tumor immunity during treatment could contribute to determining the pattern of treatment response. Implications of the different hypotheses for treatment strategies are discussed.
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Komarova, N.L., Wodarz, D. (2014). Basic Dynamics of Chronic Myeloid Leukemia During Imatinib Treatment. 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_3
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