Is the Fixed Periodic Treatment Effective for the Tumor System without Complete Information?

Jiali Wang,1,2 Yixuan Zhang,1,2 Xiaoquan Liu,1,2 Haochen Liu1,2 1School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China; 2Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, 210009, People’s Republic of ChinaCorresponden...

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Autores principales:	Wang J, Zhang Y, Liu X, Liu H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	adaptive strategy osimertinib resistance tumor evolution fixed periodic treatment plans Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/8d0e87111a09445f9834725a0e68eb9c
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spelling	oai:doaj.org-article:8d0e87111a09445f9834725a0e68eb9c2021-11-30T18:50:36ZIs the Fixed Periodic Treatment Effective for the Tumor System without Complete Information?1179-1322https://doaj.org/article/8d0e87111a09445f9834725a0e68eb9c2021-11-01T00:00:00Zhttps://www.dovepress.com/is-the-fixed-periodic-treatment-effective-for-the-tumor-system-without-peer-reviewed-fulltext-article-CMARhttps://doaj.org/toc/1179-1322Jiali Wang,1,2 Yixuan Zhang,1,2 Xiaoquan Liu,1,2 Haochen Liu1,2 1School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China; 2Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, 210009, People’s Republic of ChinaCorrespondence: Xiaoquan Liu; Haochen Liu Email lxq@cpu.edu.cn; haochenliu@cpu.edu.cnObjective: The treatment plans designed with the guidance of the mathematical model and adaptive strategy can trap tumor subpopulations in a periodic and controllable loop. But this process requires detailed information about the tumor system, which is difficult to obtain. Therefore, we wondered whether the fixed periodic treatment plans designed with the typical values of population parameters could be applied to a similar tumor system without complete information.Methods: A binary tumor system constructed by an EGFR-mutant and a KRAS-mutant cell line was used to explore the applicability of the fixed periodic treatment plans. The dynamics of this system were described by combining the Lotka-Volterra model with the framework of the nonlinear mixed-effects model. The typical values of population parameters were used to design the plans, and the robust plans were screened through parameter variation. These screened plans were examined their applicability in animal experiments and simulations.Results: In animal experiments where system parameters vary from − 30% to 30%, the “osimertinib administration, withdrawal, FK866 administration and withdrawal” plan can trap subpopulations of the system in periodic cycles. In simulation, when there was an unknown resistant subpopulation, the screened fixed periodic treatment plans can still delay the evolution of resistance. The median outcomes of screened plans were better than conventional sequential treatment in most cases. There was no significant difference between the outcomes of the screened plan with median stability and the optimal therapy. The evolutionary trajectories of these two plans were similar.Conclusion: According to the results, these fixed periodic plans should be tried in treatment even the information of the tumor system was incomplete.Keywords: adaptive strategy, osimertinib resistance, tumor evolution, fixed periodic treatment plansWang JZhang YLiu XLiu HDove Medical Pressarticleadaptive strategyosimertinib resistancetumor evolutionfixed periodic treatment plansNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancer Management and Research, Vol Volume 13, Pp 8915-8928 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	adaptive strategy osimertinib resistance tumor evolution fixed periodic treatment plans Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	adaptive strategy osimertinib resistance tumor evolution fixed periodic treatment plans Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Wang J Zhang Y Liu X Liu H Is the Fixed Periodic Treatment Effective for the Tumor System without Complete Information?
description	Jiali Wang,1,2 Yixuan Zhang,1,2 Xiaoquan Liu,1,2 Haochen Liu1,2 1School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China; 2Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, 210009, People’s Republic of ChinaCorrespondence: Xiaoquan Liu; Haochen Liu Email lxq@cpu.edu.cn; haochenliu@cpu.edu.cnObjective: The treatment plans designed with the guidance of the mathematical model and adaptive strategy can trap tumor subpopulations in a periodic and controllable loop. But this process requires detailed information about the tumor system, which is difficult to obtain. Therefore, we wondered whether the fixed periodic treatment plans designed with the typical values of population parameters could be applied to a similar tumor system without complete information.Methods: A binary tumor system constructed by an EGFR-mutant and a KRAS-mutant cell line was used to explore the applicability of the fixed periodic treatment plans. The dynamics of this system were described by combining the Lotka-Volterra model with the framework of the nonlinear mixed-effects model. The typical values of population parameters were used to design the plans, and the robust plans were screened through parameter variation. These screened plans were examined their applicability in animal experiments and simulations.Results: In animal experiments where system parameters vary from − 30% to 30%, the “osimertinib administration, withdrawal, FK866 administration and withdrawal” plan can trap subpopulations of the system in periodic cycles. In simulation, when there was an unknown resistant subpopulation, the screened fixed periodic treatment plans can still delay the evolution of resistance. The median outcomes of screened plans were better than conventional sequential treatment in most cases. There was no significant difference between the outcomes of the screened plan with median stability and the optimal therapy. The evolutionary trajectories of these two plans were similar.Conclusion: According to the results, these fixed periodic plans should be tried in treatment even the information of the tumor system was incomplete.Keywords: adaptive strategy, osimertinib resistance, tumor evolution, fixed periodic treatment plans
format	article
author	Wang J Zhang Y Liu X Liu H
author_facet	Wang J Zhang Y Liu X Liu H
author_sort	Wang J
title	Is the Fixed Periodic Treatment Effective for the Tumor System without Complete Information?
title_short	Is the Fixed Periodic Treatment Effective for the Tumor System without Complete Information?
title_full	Is the Fixed Periodic Treatment Effective for the Tumor System without Complete Information?
title_fullStr	Is the Fixed Periodic Treatment Effective for the Tumor System without Complete Information?
title_full_unstemmed	Is the Fixed Periodic Treatment Effective for the Tumor System without Complete Information?
title_sort	is the fixed periodic treatment effective for the tumor system without complete information?
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/8d0e87111a09445f9834725a0e68eb9c
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Is the Fixed Periodic Treatment Effective for the Tumor System without Complete Information?

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