title: A hybrid cellular automaton model of solid tumor growth and bioreductive drug transport.
abstract: Bioreductive drugs are a class of hypoxia selective drugs that are designed to eradicate the hypoxic fraction of solid tumors. Their activity depends upon a number of biological and pharmacological factors and we used a mathematical modeling approach to explore the dynamics of tumor growth, infusion, and penetration of the bioreductive drug Tirapazamine (TPZ). An in-silico model is implemented to calculate the tumor mass considering oxygen and glucose as key microenvironmental parameters. The next stage of the model integrated extra cellular matrix (ECM), cell-cell adhesion, and cell movement parameters as growth constraints. The tumor microenvironments strongly influenced tumor morphology and growth rates. Once the growth model was established, a hybrid model was developed to study drug dynamics inside the hypoxic regions of tumors. The model used 10, 50 and         100  \mu {\rm M}         as TPZ initial concentrations and determined TPZ pharmacokinetic (PK) (transport) and pharmacodynamics (cytotoxicity) properties inside hypoxic regions of solid tumor. The model results showed that diminished drug transport is a reason for TPZ failure and recommend the optimization of the drug transport properties in the emerging TPZ generations. The modeling approach used in this study is novel and can be a step to explore the behavioral dynamics of TPZ.
authors.affiliation: School of Computing, Engineering and Information Sciences, Northumbria University, Room PB 043, Pandon Building, Newcastle upon Tyne, Tyne and Wear NE1 8ST, United Kingdom. sonahrazia@yahoo.com
authors.forename: Nabila
authors.initials: N
authors.lastname: Kazmi
authors.forename: M A
authors.initials: MA
authors.lastname: Hossain
authors.forename: Roger M
authors.initials: RM
authors.lastname: Phillips
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001692:Biological Transport; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D016571:Neural Networks, Computer; D000077704:Tirapazamine; D014227:Triazines / Q000493:pharmacokinetics / Q000494:pharmacology; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D014227:Triazines; D000077704:Tirapazamine