title: Mathematical modeling analysis of intratumoral disposition of anticancer agents and drug delivery systems.
abstract: BACKGROUND
  Solid tumors are characterized by complex morphology. Numerous factors relating to the composition of the cells and tumor stroma, vascularization and drainage of fluids affect the local microenvironment within a specific location inside the tumor. As a result, the intratumoral drug/drug delivery system (DDS) disposition following systemic or local administration is non-homogeneous and its complexity reflects the differences in the local microenvironment. Mathematical models can be used to analyze the intratumoral drug/DDS disposition and pharmacological effects and to assist in choice of optimal anticancer treatment strategies.
  
  
  METHODS
  The mathematical models that have been applied by different research groups to describe the intratumoral disposition of anticancer drugs/DDSs are summarized in this article. The properties of these models and of their suitability for prediction of the drug/DDS intratumoral disposition and pharmacological effects are reviewed.
  
  
  CONCLUSIONS
  Currently available mathematical models appear to neglect some of the major factors that govern the drug/DDS intratumoral disposition, and apparently possess limited prediction capabilities. More sophisticated and detailed mathematical models and their extensive validation are needed for reliable prediction of different treatment scenarios and for optimization of drug treatment in the individual cancer patients.
authors: Ben-Gurion University of the Negev, Department of Clinical Biochemistry and Pharmacology, The Faculty of Health Sciences , P.O.Box 653, Beer Sheva 84105 , Israel +972 8 6477381 ; davidst@bgu.ac.il.
authors: Hen
authors: H
authors: Popilski
authors: David
authors: D
authors: Stepensky
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016503:Drug Delivery Systems; D006801:Humans; D008962:Models, Theoretical; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014018:Tissue Distribution; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents
keywords: anticancer drugs and drug delivery systems; intratumoral drug disposition; mathematical modeling; optimization of drug treatment