Multiscale Tumor Modeling With Drug Pharmacokinetic and Pharmacodynamic Profile Using Stochastic Hybrid System

Abstract

Effective cancer treatment strategy requires an understanding of cancer behavior and development across multiple temporal and spatial scales. This has resulted into a growing interest in developing multiscale mathematical models that can simulate cancer growth, development, and response to drug treatments. This study thus investigates multiscale tumor modeling that integrates drug pharmacokinetic and pharmacodynamic (PK/PD) information using stochastic hybrid system modeling framework. Specifically, (1) pathways modeled by differential equations are adopted for gene regulations at the molecular level; (2) cellular automata (CA) model is proposed for the cellular and multicellular scales. Markov chains are used to model the cell behaviors by taking into account the gene expression levels, cell cycle, and the microenvironment. The proposed model enables the prediction of tumor growth under given molecular properties, microenvironment conditions, and drug PK/PD profile. Simulation results demonstrate the effectiveness of the proposed approach and the results agree with observed tumor behaviors.