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 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.
Department of NanoMedicine and Biomedical Engineering, University of Texas Medical School at Houston, Houston, Texas, United States of America.|Brown Foundation Institute of Molecular Medicine, University of Texas Medical School at Houston, Houston, Texas, United States of America.|Department of Imaging Physics, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Zhihui
Z
Wang
Department of Pathology, University of New Mexico, Albuquerque, New Mexico, United States of America.
Romica
0000-0002-7007-1395
R
Kerketta
Department of Mathematics, California State University, Northridge, California, United States of America.
Yao-Li
YL
Chuang
Department of Pathology, University of New Mexico, Albuquerque, New Mexico, United States of America.
Prashant
P
Dogra
Department of Chemical and Biological Engineering and Center for Biomedical Engineering, University of New Mexico, Albuquerque, New Mexico, United States of America.
Joseph D
JD
Butner
Department of Chemical and Biological Engineering and Center for Biomedical Engineering, University of New Mexico, Albuquerque, New Mexico, United States of America.
Terisse A
0000-0002-4213-0749
TA
Brocato
Department of Pathology, University of New Mexico, Albuquerque, New Mexico, United States of America.
Armin
A
Day
Department of Nanomedicine, Methodist Hospital Research Institute, Houston, Texas, United States of America.
Rong
R
Xu
Department of Nanomedicine, Methodist Hospital Research Institute, Houston, Texas, United States of America.
Haifa
H
Shen
Department of Mathematics, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Eman
E
Simbawa
Department of Mathematics, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
A S
AS
Al-Fhaid
Department of Mathematics, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
S R
SR
Mahmoud
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States of America.
Steven A
SA
Curley
Department of Nanomedicine, Methodist Hospital Research Institute, Houston, Texas, United States of America.
Mauro
M
Ferrari
Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Eugene J
0000-0001-7675-3461
EJ
Koay
Department of NanoMedicine and Biomedical Engineering, University of Texas Medical School at Houston, Houston, Texas, United States of America.|Brown Foundation Institute of Molecular Medicine, University of Texas Medical School at Houston, Houston, Texas, United States of America.|Department of Imaging Physics, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.|Department of Mathematics, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Vittorio
V
Cristini
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019295:Computational Biology; D003198:Computer Simulation; D004337:Drug Carriers / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D053758:Nanoparticles / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy*; D062211:Spatio-Temporal Analysis
D000970:Antineoplastic Agents; D004337:Drug Carriers