Stochastic Dynamics of Leukemic Cells under an Intermittent Targeted Therapy

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Abstract

The evolutionary dynamics of cancerous cellpopulations in a model of Chronic Myeloid Leukemia (CML) is investigated in the presence of an intermittent targeted therapy. Cancer development and progression is modeled by simulating the stochastic evolution of initially healthy cells which can experience genetic mutations andmodify their reproductive behavior, becoming leukemic clones. Front line therapy for the treatment of patients affected by CML is based on the administration of tyrosinekinase inhibitors, namely imatinib (Gleevec) or, more recently, dasatinib or nilotinib. Despite the fact that they represent the first example of a successful molecular targeted therapy, the development of resistance to these drugs is observed in a proportion of patients, especially those inadvanced stages. In this study, we simulate an imatinib-like treatment of CML by modifying the fitness and the deathrate of cancerous cells and describe the several scenarios in the evolutionary dynamics of white blood cells as a consequence of the efficacy of the different modeled therapies.The patient response to the therapy is investigated by simulating a drug administration following a continuous orpulsed time scheduling. A permanent disappearance of leukemic clones is achieved with a continuous therapy. This theoretical behavior is in a good agreement with thatobserved in previous clinical investigations. However, these findings demonstrate that an intermittent therapycould represent a valid alternative in patients with high risk of toxicity. A suitable tuned pulsed therapy can also reducethe probability of developing resistance.
Lingua originaleEnglish
pagine (da-a)203-210
Numero di pagine8
RivistaTHEORY IN BIOSCIENCES
Volume130
Stato di pubblicazionePublished - 2011

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All Science Journal Classification (ASJC) codes

  • Statistics and Probability
  • Ecology, Evolution, Behavior and Systematics
  • Applied Mathematics

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