Modelling and Simulation of Drug Delivery Systems for the Treatment of Acute Myeloid Leukemia
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abstract
Cancer, including Acute Myeloid Leukemia (AML), results from the loss of control of the cell cycle where the cells proliferate abnormally. A complicated network of reactions and cell-signaling pathways are involved in this process of leukemogenesis. The actions and targeting of chemotherapeutic treatments to interfere with this abnormal cell signaling are equally as complicated in vivo. Herein, we attempt to describe this process through the development of a dynamic model for the in vivo actions of a single chemotherapeutic drug, cytarabine (ARA-C), used routinely for the treatment of AML. The proposed model combines the actions on the cell cycle, which is the target of the drug, with pharmacokinetic and pharmacodynamic aspects in order to provide a comprehensive description of drug diffusion and action after administration. The model also takes into account patient factors such as age, sex, weight and height in an attempt to gain insights towards optimisation of individual treatment protocols for effective patient-specific and leukemia-specific therapy that can also minimise toxicity. This model may then be used as a means to obtain insight to the chemotherapy procedure and used as a predictive tool of the patient response during treatment, similar to what we have previously demonstrated for breast cancer treatment (Dua et al. 2008; Dua et.al. 2005). 2011 Springer-Verlag Berlin Heidelberg.
