Theory and Experimental Validation of a Spatio-temporal Model of Chemotherapy Transport to Enhance Tumor Cell Kill

Cancer treatment efficacy can be significantly enhanced through the elution of drug from nano-carriers that can temporarily stay in the tumor vasculature. Here we present a relatively simple yet powerful mathematical model that accounts for both spatial and temporal heterogeneities of drug dosing to...

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Bibliographic Details
Published in:PLoS computational biology 2016-06, Vol.12 (6), p.e1004969
Main Authors: Wang, Zhihui, Kerketta, Romica, Chuang, Yao-Li, Dogra, Prashant, Butner, Joseph D, Brocato, Terisse A, Day, Armin, Xu, Rong, Shen, Haifa, Simbawa, Eman, Al-Fhaid, A S, Mahmoud, S R, Curley, Steven A, Ferrari, Mauro, Koay, Eugene J, Cristini, Vittorio
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacokinetics
Antineoplastic Agents - therapeutic use
Biology and Life Sciences
Blood
Cancer
Cancer cells
Cancer therapies
Chemotherapy
Computational Biology
Computer Simulation
Drug Carriers - pharmacokinetics
Drug Carriers - therapeutic use
Drug delivery systems
Drug dosages
Female
Histopathology
Hypotheses
Mathematical models
Medicine and Health Sciences
Methods
Mice
Mice, Inbred BALB C
Models, Biological
Nanoparticles - therapeutic use
Neoplasms - drug therapy
Physical properties
Prevention
Software
Spatio-Temporal Analysis
Tumors
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Summary:Cancer treatment efficacy can be significantly enhanced through the elution of drug from nano-carriers that can temporarily stay in the tumor vasculature. Here we present a relatively simple yet powerful mathematical model that accounts for both spatial and temporal heterogeneities of drug dosing to help explain, examine, and prove this concept. We find that the delivery of systemic chemotherapy through a certain form of nano-carriers would have enhanced tumor kill by a factor of 2 to 4 over the standard therapy that the patients actually received. We also find that targeting blood volume fraction (a parameter of the model) through vascular normalization can achieve more effective drug delivery and tumor kill. More importantly, this model only requires a limited number of parameters which can all be readily assessed from standard clinical diagnostic measurements (e.g., histopathology and CT). This addresses an important challenge in current translational research and justifies further development of the model towards clinical translation.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1004969