Mathematical modeling analysis of intratumoral disposition of anticancer agents and drug delivery systems

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords:

• anticancer drugs and drug delivery systems
• intratumoral drug disposition
• mathematical modeling
• optimization of drug treatment

Declaration of interest

This research project of analysis and mathematical modeling of intratumoral drug/drug delivery system disposition was funded by the US–Israel Binational Science Foundation grant No 2013/131. D Stepensky serves as a consultant of LipoCure Ltd, Jerusalem, Israel, that develops proprietary liposome-based nanodrugs. Except of this, the authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents, received or pending, or royalties.

Notes

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