A phenotype-structured mathematical model for the influence of hypoxia on oncolytic virotherapy

ronment, which reduce the ability of the virus to infect cancer cells. In this work, we focus on the influence of hypoxia on this therapy and develop a novel continuous mathematical model that considers both the spatial and epigenetic heterogeneity of the tumour. We investigate how oxygen gradients...

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Autores: Morselli, David, Chiari, Giulia, Frascoli, Federico, Delitala, Marcello Edoardo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Basque Center for Applied Mathematics (BCAM)
Repositorio:BIRD. BCAM's Institutional Repository Data
OAI Identifier:oai:bird.bcamath.org:20.500.11824/2128
Acceso en línea:http://hdl.handle.net/20.500.11824/2128
https://doi.org/10.1016/j.mbs.2025.109570
Access Level:acceso abierto
Palabra clave:Oncolytic virus
Hypoxia
Tumour phenotypic heterogeneity
Continuous structured models
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spelling A phenotype-structured mathematical model for the influence of hypoxia on oncolytic virotherapyMorselli, DavidChiari, GiuliaFrascoli, FedericoDelitala, Marcello EdoardoOncolytic virusHypoxiaTumour phenotypic heterogeneityContinuous structured modelsronment, which reduce the ability of the virus to infect cancer cells. In this work, we focus on the influence of hypoxia on this therapy and develop a novel continuous mathematical model that considers both the spatial and epigenetic heterogeneity of the tumour. We investigate how oxygen gradients within tumours affect the spatial distribution and replication of both the tumour and oncolytic viruses, focusing on regions of severe hypoxia versus normoxic areas. Additionally, we analyse the evolutionary dynamics of tumour cells under hypoxic conditions and their influence on susceptibility to viral infection. Our findings show that the reduced metabolic activity of hypoxic cells may significantly impact the virotherapy effectiveness; the knowledge of the tumour’s oxygenation could, therefore, suggest the most suitable type of virus to optimise the outcome. The combination of numerical simulations and theoretical results for the model equilibrium values allows us to elucidate the complex interplay between viruses, tumour evolution and oxygen dynamics, ultimately contributing to developing more effective and personalised cancer treatments.202520252025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/20.500.11824/2128https://doi.org/10.1016/j.mbs.2025.109570reponame:BIRD. BCAM's Institutional Repository Datainstname:Basque Center for Applied Mathematics (BCAM)Ingléshttps://www.sciencedirect.com/science/article/pii/S0025556425001968?lid=jua9g5tkojjo&utm_source=braze&utm_medium=email&utm_campaign=STMJ_220042_AUTH_SERV_PPUB&utm_content=07bab9e4-c31e-408b-afa5-1c9ca0f269ca&utm_term=07bab9e4-c31e-408b-afa5-1c9ca0f269ca&DGCID=STMJ_220042_AUTH_SERV_PPUBinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/CEX2021-001142-SReconocimiento-NoComercial-CompartirIgual 3.0 Españahttp://creativecommons.org/licenses/by-nc-sa/3.0/es/info:eu-repo/semantics/openAccessoai:bird.bcamath.org:20.500.11824/21282026-06-19T12:47:47Z
dc.title.none.fl_str_mv A phenotype-structured mathematical model for the influence of hypoxia on oncolytic virotherapy
title A phenotype-structured mathematical model for the influence of hypoxia on oncolytic virotherapy
spellingShingle A phenotype-structured mathematical model for the influence of hypoxia on oncolytic virotherapy
Morselli, David
Oncolytic virus
Hypoxia
Tumour phenotypic heterogeneity
Continuous structured models
title_short A phenotype-structured mathematical model for the influence of hypoxia on oncolytic virotherapy
title_full A phenotype-structured mathematical model for the influence of hypoxia on oncolytic virotherapy
title_fullStr A phenotype-structured mathematical model for the influence of hypoxia on oncolytic virotherapy
title_full_unstemmed A phenotype-structured mathematical model for the influence of hypoxia on oncolytic virotherapy
title_sort A phenotype-structured mathematical model for the influence of hypoxia on oncolytic virotherapy
dc.creator.none.fl_str_mv Morselli, David
Chiari, Giulia
Frascoli, Federico
Delitala, Marcello Edoardo
author Morselli, David
author_facet Morselli, David
Chiari, Giulia
Frascoli, Federico
Delitala, Marcello Edoardo
author_role author
author2 Chiari, Giulia
Frascoli, Federico
Delitala, Marcello Edoardo
author2_role author
author
author
dc.subject.none.fl_str_mv Oncolytic virus
Hypoxia
Tumour phenotypic heterogeneity
Continuous structured models
topic Oncolytic virus
Hypoxia
Tumour phenotypic heterogeneity
Continuous structured models
description ronment, which reduce the ability of the virus to infect cancer cells. In this work, we focus on the influence of hypoxia on this therapy and develop a novel continuous mathematical model that considers both the spatial and epigenetic heterogeneity of the tumour. We investigate how oxygen gradients within tumours affect the spatial distribution and replication of both the tumour and oncolytic viruses, focusing on regions of severe hypoxia versus normoxic areas. Additionally, we analyse the evolutionary dynamics of tumour cells under hypoxic conditions and their influence on susceptibility to viral infection. Our findings show that the reduced metabolic activity of hypoxic cells may significantly impact the virotherapy effectiveness; the knowledge of the tumour’s oxygenation could, therefore, suggest the most suitable type of virus to optimise the outcome. The combination of numerical simulations and theoretical results for the model equilibrium values allows us to elucidate the complex interplay between viruses, tumour evolution and oxygen dynamics, ultimately contributing to developing more effective and personalised cancer treatments.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.11824/2128
https://doi.org/10.1016/j.mbs.2025.109570
url http://hdl.handle.net/20.500.11824/2128
https://doi.org/10.1016/j.mbs.2025.109570
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://www.sciencedirect.com/science/article/pii/S0025556425001968?lid=jua9g5tkojjo&utm_source=braze&utm_medium=email&utm_campaign=STMJ_220042_AUTH_SERV_PPUB&utm_content=07bab9e4-c31e-408b-afa5-1c9ca0f269ca&utm_term=07bab9e4-c31e-408b-afa5-1c9ca0f269ca&DGCID=STMJ_220042_AUTH_SERV_PPUB
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/CEX2021-001142-S
dc.rights.none.fl_str_mv Reconocimiento-NoComercial-CompartirIgual 3.0 España
http://creativecommons.org/licenses/by-nc-sa/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Reconocimiento-NoComercial-CompartirIgual 3.0 España
http://creativecommons.org/licenses/by-nc-sa/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:BIRD. BCAM's Institutional Repository Data
instname:Basque Center for Applied Mathematics (BCAM)
instname_str Basque Center for Applied Mathematics (BCAM)
reponame_str BIRD. BCAM's Institutional Repository Data
collection BIRD. BCAM's Institutional Repository Data
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repository.mail.fl_str_mv
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