Mathematical models of the steps involved in the systemic delivery of a chemotherapeutic to a solid tumor: From circulation to survival

TY - JOUR

T1 - Mathematical models of the steps involved in the systemic delivery of a chemotherapeutic to a solid tumor

T2 - From circulation to survival

AU - Ulmschneider, Martin B

AU - Searson, Peter C

N1 - Copyright © 2015 Elsevier B.V. All rights reserved.

PY - 2015/8/28

Y1 - 2015/8/28

N2 - The efficacy of an intravenously administered chemotherapeutic for treatment of a solid tumor is dependent on a sequence of steps, including circulation, extravasation by the enhanced permeability and retention effect, transport in the tumor microenvironment, the mechanism of cellular uptake and trafficking, and the mechanism of drug action. These steps are coupled since the time dependent concentration in circulation determines the concentration and distribution in the tumor microenvironment, and hence the amount taken up by individual cells within the tumor. Models have been developed for each of the steps in the delivery process although their predictive power remains limited. Advances in our understanding of the steps in the delivery process will result in refined models with improvements in predictive power and ultimately allow the development of integrated models that link systemic administration of a drug to the probability of survival. Integrated models that predict outcomes based on patient specific data could be used to select the optimum therapeutic regimens. Here we present an overview of current models for the steps in the delivery process and highlight knowledge gaps that are key to developing integrated models.

AB - The efficacy of an intravenously administered chemotherapeutic for treatment of a solid tumor is dependent on a sequence of steps, including circulation, extravasation by the enhanced permeability and retention effect, transport in the tumor microenvironment, the mechanism of cellular uptake and trafficking, and the mechanism of drug action. These steps are coupled since the time dependent concentration in circulation determines the concentration and distribution in the tumor microenvironment, and hence the amount taken up by individual cells within the tumor. Models have been developed for each of the steps in the delivery process although their predictive power remains limited. Advances in our understanding of the steps in the delivery process will result in refined models with improvements in predictive power and ultimately allow the development of integrated models that link systemic administration of a drug to the probability of survival. Integrated models that predict outcomes based on patient specific data could be used to select the optimum therapeutic regimens. Here we present an overview of current models for the steps in the delivery process and highlight knowledge gaps that are key to developing integrated models.

KW - Animals

KW - Antineoplastic Agents/pharmacokinetics

KW - Biological Transport

KW - Humans

KW - Models, Biological

KW - Neoplasms/blood supply

U2 - 10.1016/j.jconrel.2015.06.026

DO - 10.1016/j.jconrel.2015.06.026

M3 - Review article

C2 - 26103439

SN - 0168-3659

VL - 212

SP - 78

EP - 84

JO - Journal of controlled release : official journal of the Controlled Release Society

JF - Journal of controlled release : official journal of the Controlled Release Society

ER -