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Numerical simulation of vascular tumour growth under antiangiogenic treatment: addressing the paradigm of single-agent bevacizumab therapy with the use of experimental data

BACKGROUND: Antiangiogenic agents have been recently added to the oncological armamentarium with bevacizumab probably being the most popular representative in current clinical practice. The elucidation of the mode of action of these agents is a prerequisite for personalized prediction of antiangioge...

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Autores principales: Argyri, Katerina D., Dionysiou, Dimitra D., Misichroni, Fay D., Stamatakos, Georgios S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804544/
https://www.ncbi.nlm.nih.gov/pubmed/27005569
http://dx.doi.org/10.1186/s13062-016-0114-9
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author Argyri, Katerina D.
Dionysiou, Dimitra D.
Misichroni, Fay D.
Stamatakos, Georgios S.
author_facet Argyri, Katerina D.
Dionysiou, Dimitra D.
Misichroni, Fay D.
Stamatakos, Georgios S.
author_sort Argyri, Katerina D.
collection PubMed
description BACKGROUND: Antiangiogenic agents have been recently added to the oncological armamentarium with bevacizumab probably being the most popular representative in current clinical practice. The elucidation of the mode of action of these agents is a prerequisite for personalized prediction of antiangiogenic treatment response and selection of patients who may benefit from this kind of therapy. To this end, having used as a basis a preexisting continuous vascular tumour growth model which addresses the targeted nature of antiangiogenic treatment, we present a paper characterized by the following three features. First, the integration of a two-compartmental bevacizumab specific pharmacokinetic module into the core of the aforementioned preexisting model. Second, its mathematical modification in order to reproduce the asymptotic behaviour of tumour volume in the theoretical case of a total destruction of tumour neovasculature. Third, the exploitation of a range of published animal datasets pertaining to antitumour efficacy of bevacizumab on various tumour types (breast, lung, head and neck, colon). RESULTS: Results for both the unperturbed growth and the treatment module reveal qualitative similarities with experimental observations establishing the biologically acceptable behaviour of the model. The dynamics of the untreated tumour has been studied via a parameter analysis, revealing the role of each relevant input parameter to tumour evolution. The combined effect of endogenous proangiogenic and antiangiogenic factors on the angiogenic potential of a tumour is also studied, in order to capture the dynamics of molecular competition between the two key-players of tumoural angiogenesis. The adopted methodology also allows accounting for the newly recognized direct antitumour effect of the specific agent. CONCLUSIONS: Interesting observations have been made, suggesting a potential size-dependent tumour response to different treatment modalities and determining the relative timing of cytotoxic versus antiangiogenic agents administration. Insight into the comparative effectiveness of different antiangiogenic treatment strategies is revealed. The results of a series of in vivo experiments in mice bearing diverse types of tumours (breast, lung, head and neck, colon) and treated with bevacizumab are successfully reproduced, supporting thus the validity of the underlying model. REVIEWERS: This article was reviewed by L. Hanin, T. Radivoyevitch and L. Edler.
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spelling pubmed-48045442016-03-23 Numerical simulation of vascular tumour growth under antiangiogenic treatment: addressing the paradigm of single-agent bevacizumab therapy with the use of experimental data Argyri, Katerina D. Dionysiou, Dimitra D. Misichroni, Fay D. Stamatakos, Georgios S. Biol Direct Research BACKGROUND: Antiangiogenic agents have been recently added to the oncological armamentarium with bevacizumab probably being the most popular representative in current clinical practice. The elucidation of the mode of action of these agents is a prerequisite for personalized prediction of antiangiogenic treatment response and selection of patients who may benefit from this kind of therapy. To this end, having used as a basis a preexisting continuous vascular tumour growth model which addresses the targeted nature of antiangiogenic treatment, we present a paper characterized by the following three features. First, the integration of a two-compartmental bevacizumab specific pharmacokinetic module into the core of the aforementioned preexisting model. Second, its mathematical modification in order to reproduce the asymptotic behaviour of tumour volume in the theoretical case of a total destruction of tumour neovasculature. Third, the exploitation of a range of published animal datasets pertaining to antitumour efficacy of bevacizumab on various tumour types (breast, lung, head and neck, colon). RESULTS: Results for both the unperturbed growth and the treatment module reveal qualitative similarities with experimental observations establishing the biologically acceptable behaviour of the model. The dynamics of the untreated tumour has been studied via a parameter analysis, revealing the role of each relevant input parameter to tumour evolution. The combined effect of endogenous proangiogenic and antiangiogenic factors on the angiogenic potential of a tumour is also studied, in order to capture the dynamics of molecular competition between the two key-players of tumoural angiogenesis. The adopted methodology also allows accounting for the newly recognized direct antitumour effect of the specific agent. CONCLUSIONS: Interesting observations have been made, suggesting a potential size-dependent tumour response to different treatment modalities and determining the relative timing of cytotoxic versus antiangiogenic agents administration. Insight into the comparative effectiveness of different antiangiogenic treatment strategies is revealed. The results of a series of in vivo experiments in mice bearing diverse types of tumours (breast, lung, head and neck, colon) and treated with bevacizumab are successfully reproduced, supporting thus the validity of the underlying model. REVIEWERS: This article was reviewed by L. Hanin, T. Radivoyevitch and L. Edler. BioMed Central 2016-03-22 /pmc/articles/PMC4804544/ /pubmed/27005569 http://dx.doi.org/10.1186/s13062-016-0114-9 Text en © Argyri et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Argyri, Katerina D.
Dionysiou, Dimitra D.
Misichroni, Fay D.
Stamatakos, Georgios S.
Numerical simulation of vascular tumour growth under antiangiogenic treatment: addressing the paradigm of single-agent bevacizumab therapy with the use of experimental data
title Numerical simulation of vascular tumour growth under antiangiogenic treatment: addressing the paradigm of single-agent bevacizumab therapy with the use of experimental data
title_full Numerical simulation of vascular tumour growth under antiangiogenic treatment: addressing the paradigm of single-agent bevacizumab therapy with the use of experimental data
title_fullStr Numerical simulation of vascular tumour growth under antiangiogenic treatment: addressing the paradigm of single-agent bevacizumab therapy with the use of experimental data
title_full_unstemmed Numerical simulation of vascular tumour growth under antiangiogenic treatment: addressing the paradigm of single-agent bevacizumab therapy with the use of experimental data
title_short Numerical simulation of vascular tumour growth under antiangiogenic treatment: addressing the paradigm of single-agent bevacizumab therapy with the use of experimental data
title_sort numerical simulation of vascular tumour growth under antiangiogenic treatment: addressing the paradigm of single-agent bevacizumab therapy with the use of experimental data
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804544/
https://www.ncbi.nlm.nih.gov/pubmed/27005569
http://dx.doi.org/10.1186/s13062-016-0114-9
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