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Bridging Scales: a Hybrid Model to Simulate Vascular Tumor Growth and Treatment Response

Cancer is a disease driven by random DNA mutations and the interaction of many complex phenomena. To improve the understanding and ultimately find more effective treatments, researchers leverage computer simulations mimicking the tumor growth in silico. The challenge here is to account for the many...

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Autores principales: Duswald, Tobias, Lima, Ernesto A.B.F., Oden, J. Tinsley, Wohlmuth, Barbara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cornell University 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10274951/
https://www.ncbi.nlm.nih.gov/pubmed/37332572
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author Duswald, Tobias
Lima, Ernesto A.B.F.
Oden, J. Tinsley
Wohlmuth, Barbara
author_facet Duswald, Tobias
Lima, Ernesto A.B.F.
Oden, J. Tinsley
Wohlmuth, Barbara
author_sort Duswald, Tobias
collection PubMed
description Cancer is a disease driven by random DNA mutations and the interaction of many complex phenomena. To improve the understanding and ultimately find more effective treatments, researchers leverage computer simulations mimicking the tumor growth in silico. The challenge here is to account for the many phenomena influencing the disease progression and treatment protocols. This work introduces a computational model to simulate vascular tumor growth and the response to drug treatments in 3D. It consists of two agent-based models for the tumor cells and the vasculature. Moreover, partial differential equations govern the diffusive dynamics of the nutrients, the vascular endothelial growth factor, and two cancer drugs. The model focuses explicitly on breast cancer cells over-expressing HER2 receptors and a treatment combining standard chemotherapy (Doxorubicin) and monoclonal antibodies with anti-angiogenic properties (Trastuzumab). However, large parts of the model generalize to other scenarios. We show that the model qualitatively captures the effects of the combination therapy by comparing our simulation results with previously published pre-clinical data. Furthermore, we demonstrate the scalability of the model and the associated C++ code by simulating a vascular tumor occupying a volume of 400mm(3) using a total of 92.5 million agents.
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spelling pubmed-102749512023-06-17 Bridging Scales: a Hybrid Model to Simulate Vascular Tumor Growth and Treatment Response Duswald, Tobias Lima, Ernesto A.B.F. Oden, J. Tinsley Wohlmuth, Barbara ArXiv Article Cancer is a disease driven by random DNA mutations and the interaction of many complex phenomena. To improve the understanding and ultimately find more effective treatments, researchers leverage computer simulations mimicking the tumor growth in silico. The challenge here is to account for the many phenomena influencing the disease progression and treatment protocols. This work introduces a computational model to simulate vascular tumor growth and the response to drug treatments in 3D. It consists of two agent-based models for the tumor cells and the vasculature. Moreover, partial differential equations govern the diffusive dynamics of the nutrients, the vascular endothelial growth factor, and two cancer drugs. The model focuses explicitly on breast cancer cells over-expressing HER2 receptors and a treatment combining standard chemotherapy (Doxorubicin) and monoclonal antibodies with anti-angiogenic properties (Trastuzumab). However, large parts of the model generalize to other scenarios. We show that the model qualitatively captures the effects of the combination therapy by comparing our simulation results with previously published pre-clinical data. Furthermore, we demonstrate the scalability of the model and the associated C++ code by simulating a vascular tumor occupying a volume of 400mm(3) using a total of 92.5 million agents. Cornell University 2023-06-09 /pmc/articles/PMC10274951/ /pubmed/37332572 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Duswald, Tobias
Lima, Ernesto A.B.F.
Oden, J. Tinsley
Wohlmuth, Barbara
Bridging Scales: a Hybrid Model to Simulate Vascular Tumor Growth and Treatment Response
title Bridging Scales: a Hybrid Model to Simulate Vascular Tumor Growth and Treatment Response
title_full Bridging Scales: a Hybrid Model to Simulate Vascular Tumor Growth and Treatment Response
title_fullStr Bridging Scales: a Hybrid Model to Simulate Vascular Tumor Growth and Treatment Response
title_full_unstemmed Bridging Scales: a Hybrid Model to Simulate Vascular Tumor Growth and Treatment Response
title_short Bridging Scales: a Hybrid Model to Simulate Vascular Tumor Growth and Treatment Response
title_sort bridging scales: a hybrid model to simulate vascular tumor growth and treatment response
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10274951/
https://www.ncbi.nlm.nih.gov/pubmed/37332572
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