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Because cancer usually involves multiple genes and pathways, combination therapy is considered as a promising approach for cancer treatment. However, when multiple drugs are taken by a patient simultaneously, toxicity becomes a concern. A potential solution is to give the drugs sequentially rather than simultaneously. In this study, we try to explore the feasibility of such an approach. Specifically,...
The complexity of biological signaling networks, especially the uncertainties associated with the model parameters, present challenges for understanding the behavior of such networks and hence hamper the translation of the modeling study into drug development process. Sensitivity analysis can help to determine which parameters are the "key drivers" of the model's output. How to tailor the...
In recent years, targeted therapy to treat cancer is gaining popularity. However, how to quantitatively and dynamically analyze the drug effect for molecularly targeted agents is quite different from traditional cytotoxic drugs. A novel preclinical model combining experimental methods and theoretical analysis is proposed to investigate the mechanisms of action and identify pharmacodynamic characteristic...
A novel preclinical model combining experimental methods and theoretical analysis is proposed to investigate the mechanism of action and identify pharmacodynamic characteristic of a drug. Instead of fixed time point analysis of the drug exposure to drug effect, the time course of drug effect for different doses are quantitatively studied on cell line-based platforms using Kalman filter, where tumor...
This paper proposes a framework to study the drug effect at the molecular level in order to address the following question of current interest in the drug community: Given a fixed total delivered drug, which is better, frequent small or infrequent large drug dosages? A hybrid system model is proposed to link the drug's pharmacokinetic and pharmacodynamic information, and allows the drug effects for...
In this paper, we propose to study the treatment and drug effects at the molecular level using a hybrid system model. Specifically, we propose a generic piecewise linear model to analyze drug effects on the state of the genes in a genetic regulatory network. We intend to answer the following question: given an initial state, would a treatment or drug (control input) drive the target gene to a new...
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