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Network-Based Mechanistic Model for Tumor Growth Development

Danilo Ribeiro and Jose M. Pinto. Othmer-Jacobs Department of Chemical and Biological Engineering, Polytechnic University, Six Metrotech Center, Brooklyn, NY 11201

Cancer chemotherapy complexity ranges from the routes that the chemotherapeutic drug must follow before reaching the tumor site (pharmacokinetics), and by the drug effects on tumor depletion (pharmacodynamics). Previous researchers, in their majority, have focused either on the pharmacokinetics (PK) or on the pharmacodynamics (PD) aspects of chemotherapy.

In a first stage, we have successfully improved a three compartment PK/PD model for liposomal doxorubicin proposed by Harashima et al. (1999). However, our model lacks PD complexity, since the tumor is represented as a single variable parametric model that only accounts for tumor cells.

The objective of this work is the development of a mechanistic model that accounts for the p53 gene regulation inside the tumor core; in addition, its dynamics is studied under drug administration. Researchers have focused on the importance of the p53 network in tumor control and development. p53 sits as the main hub of a wide network of intracellular and extracellular inputs (Oren et al., 2002) that control genomic integrity (Bargonetti et al., 2002), regulating caspase and apoptosis activity and tumor development. Kohn (1999) proposed a dense network for p53 while Chickarmane et al. (2005), Ciliberto et al. (2005) and Oren et al. (2002), among others, have proposed simpler sub networks for the p53 signaling pathways.


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Chickarmane, V., Nadim, A., Ray, A., and Sauro, H.M. (2005). A p53 Oscillator Model of DNA Break Repair Control. arXiv:q-bio.MN/0510002 v1.

Ciliberto, A., Novak, B., and Tyson, J.J. (2005). Steady States and Oscillations in the p53/Mdm2 Network. Cell Cycle 4 107-112.

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