Oscillatory dynamics in a model of vascular tumour growth -- implications for chemotherapy

Background Investigations of solid tumours suggest that vessel occlusion may occur when increased pressure from the tumour mass is exerted on the vessel walls. Since immature vessels are frequently found in tumours and may be particularly sensitive, such occlusion may impair tumour blood flow and h...

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Main Authors: Stamper, I, Owen, M, Maini, P, Byrne, H
Format: Journal article
Published: Biomed Central Ltd 2010
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author Stamper, I
Owen, M
Maini, P
Byrne, H
author_facet Stamper, I
Owen, M
Maini, P
Byrne, H
author_sort Stamper, I
collection OXFORD
description Background Investigations of solid tumours suggest that vessel occlusion may occur when increased pressure from the tumour mass is exerted on the vessel walls. Since immature vessels are frequently found in tumours and may be particularly sensitive, such occlusion may impair tumour blood flow and have a negative impact on therapeutic outcome. In order to study the effects that occlusion may have on tumour growth patterns and therapeutic response, in this paper we develop and investigate a continuum model of vascular tumour growth. Results By analysing a spatially uniform submodel, we identify regions of parameter space in which the combination of tumour cell proliferation and vessel occlusion give rise to sustained temporal oscillations in the tumour cell population and in the vessel density. Alternatively, if the vessels are assumed to be less prone to collapse, stable steady state solutions are observed. When spatial effects are considered, the pattern of tumour invasion depends on the dynamics of the spatially uniform submodel. If the submodel predicts a stable steady state, then steady travelling waves are observed in the full model, and the system evolves to the same stable steady state behind the invading front. When the submodel yields oscillatory behaviour, the full model produces periodic travelling waves. The stability of the waves (which can be predicted by approximating the system as one of λ-ω type) dictates whether the waves develop into regular or irregular spatio-temporal oscillations. Simulations of chemotherapy reveal that treatment outcome depends crucially on the underlying tumour growth dynamics. In particular, if the dynamics are oscillatory, then therapeutic efficacy is difficult to assess since the fluctuations in the size of the tumour cell population are enhanced, compared to untreated controls. Conclusions We have developed a mathematical model of vascular tumour growth formulated as a system of partial differential equations (PDEs). Employing a combination of numerical and analytical techniques, we demonstrate how the spatio-temporal dynamics of the untreated tumour may influence its response to chemotherapy. Reviewers This manuscript was reviewed by Professor Zvia Agur and Professor Marek Kimmel.
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spelling oxford-uuid:3c7c0469-44b5-448b-baa2-09d4a4499c012022-03-26T14:14:02ZOscillatory dynamics in a model of vascular tumour growth -- implications for chemotherapyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3c7c0469-44b5-448b-baa2-09d4a4499c01Mathematical Institute - ePrintsBiomed Central Ltd2010Stamper, IOwen, MMaini, PByrne, HBackground Investigations of solid tumours suggest that vessel occlusion may occur when increased pressure from the tumour mass is exerted on the vessel walls. Since immature vessels are frequently found in tumours and may be particularly sensitive, such occlusion may impair tumour blood flow and have a negative impact on therapeutic outcome. In order to study the effects that occlusion may have on tumour growth patterns and therapeutic response, in this paper we develop and investigate a continuum model of vascular tumour growth. Results By analysing a spatially uniform submodel, we identify regions of parameter space in which the combination of tumour cell proliferation and vessel occlusion give rise to sustained temporal oscillations in the tumour cell population and in the vessel density. Alternatively, if the vessels are assumed to be less prone to collapse, stable steady state solutions are observed. When spatial effects are considered, the pattern of tumour invasion depends on the dynamics of the spatially uniform submodel. If the submodel predicts a stable steady state, then steady travelling waves are observed in the full model, and the system evolves to the same stable steady state behind the invading front. When the submodel yields oscillatory behaviour, the full model produces periodic travelling waves. The stability of the waves (which can be predicted by approximating the system as one of λ-ω type) dictates whether the waves develop into regular or irregular spatio-temporal oscillations. Simulations of chemotherapy reveal that treatment outcome depends crucially on the underlying tumour growth dynamics. In particular, if the dynamics are oscillatory, then therapeutic efficacy is difficult to assess since the fluctuations in the size of the tumour cell population are enhanced, compared to untreated controls. Conclusions We have developed a mathematical model of vascular tumour growth formulated as a system of partial differential equations (PDEs). Employing a combination of numerical and analytical techniques, we demonstrate how the spatio-temporal dynamics of the untreated tumour may influence its response to chemotherapy. Reviewers This manuscript was reviewed by Professor Zvia Agur and Professor Marek Kimmel.
spellingShingle Stamper, I
Owen, M
Maini, P
Byrne, H
Oscillatory dynamics in a model of vascular tumour growth -- implications for chemotherapy
title Oscillatory dynamics in a model of vascular tumour growth -- implications for chemotherapy
title_full Oscillatory dynamics in a model of vascular tumour growth -- implications for chemotherapy
title_fullStr Oscillatory dynamics in a model of vascular tumour growth -- implications for chemotherapy
title_full_unstemmed Oscillatory dynamics in a model of vascular tumour growth -- implications for chemotherapy
title_short Oscillatory dynamics in a model of vascular tumour growth -- implications for chemotherapy
title_sort oscillatory dynamics in a model of vascular tumour growth implications for chemotherapy
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