Efficient Radial-Shell Model for 3D Tumor Spheroid Dynamics with Radiotherapy
Understanding the complex dynamics of tumor growth to develop more efficient therapeutic strategies is one of the most challenging problems in biomedicine. Three-dimensional (3D) tumor spheroids, reflecting avascular microregions within a tumor, are an advanced in vitro model system to assess the cu...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/23/5645 |
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| author | Florian Franke Soňa Michlíková Sebastian Aland Leoni A. Kunz-Schughart Anja Voss-Böhme Steffen Lange |
| author_facet | Florian Franke Soňa Michlíková Sebastian Aland Leoni A. Kunz-Schughart Anja Voss-Böhme Steffen Lange |
| author_sort | Florian Franke |
| collection | DOAJ |
| description | Understanding the complex dynamics of tumor growth to develop more efficient therapeutic strategies is one of the most challenging problems in biomedicine. Three-dimensional (3D) tumor spheroids, reflecting avascular microregions within a tumor, are an advanced in vitro model system to assess the curative effect of combinatorial radio(chemo)therapy. Tumor spheroids exhibit particular crucial pathophysiological characteristics such as a radial oxygen gradient that critically affect the sensitivity of the malignant cell population to treatment. However, spheroid experiments remain laborious, and determining long-term radio(chemo)therapy outcomes is challenging. Mathematical models of spheroid dynamics have the potential to enhance the informative value of experimental data, and can support study design; however, they typically face one of two limitations: while non-spatial models are computationally cheap, they lack the spatial resolution to predict oxygen-dependent radioresponse, whereas models that describe spatial cell dynamics are computationally expensive and often heavily parameterized, impeding the required calibration to experimental data. Here, we present an effectively one-dimensional mathematical model based on the cell dynamics within and across radial spheres which fully incorporates the 3D dynamics of tumor spheroids by exploiting their approximate rotational symmetry. We demonstrate that this radial-shell (RS) model reproduces experimental spheroid growth curves of several cell lines with and without radiotherapy, showing equal or better performance than published models such as 3D agent-based models. Notably, the RS model is sufficiently efficient to enable multi-parametric optimization within previously reported and/or physiologically reasonable ranges based on experimental data. Analysis of the model reveals that the characteristic change of dynamics observed in experiments at small spheroid volume originates from the spatial scale of cell interactions. Based on the calibrated parameters, we predict the spheroid volumes at which this behavior should be observable. Finally, we demonstrate how the generic parameterization of the model allows direct parameter transfer to 3D agent-based models. |
| first_indexed | 2024-03-09T01:53:27Z |
| format | Article |
| id | doaj.art-05ba986bf3684b8185dbd213e524293c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T01:53:27Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-05ba986bf3684b8185dbd213e524293c2023-12-08T15:12:49ZengMDPI AGCancers2072-66942023-11-011523564510.3390/cancers15235645Efficient Radial-Shell Model for 3D Tumor Spheroid Dynamics with RadiotherapyFlorian Franke0Soňa Michlíková1Sebastian Aland2Leoni A. Kunz-Schughart3Anja Voss-Böhme4Steffen Lange5DataMedAssist Group, HTW Dresden—University of Applied Sciences, 01069 Dresden, GermanyOncoRay—National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden—Rossendorf, 01307 Dresden, GermanyFaculty of Informatics/Mathematics, HTW Dresden—University of Applied Sciences, 01069 Dresden, GermanyOncoRay—National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden—Rossendorf, 01307 Dresden, GermanyDataMedAssist Group, HTW Dresden—University of Applied Sciences, 01069 Dresden, GermanyDataMedAssist Group, HTW Dresden—University of Applied Sciences, 01069 Dresden, GermanyUnderstanding the complex dynamics of tumor growth to develop more efficient therapeutic strategies is one of the most challenging problems in biomedicine. Three-dimensional (3D) tumor spheroids, reflecting avascular microregions within a tumor, are an advanced in vitro model system to assess the curative effect of combinatorial radio(chemo)therapy. Tumor spheroids exhibit particular crucial pathophysiological characteristics such as a radial oxygen gradient that critically affect the sensitivity of the malignant cell population to treatment. However, spheroid experiments remain laborious, and determining long-term radio(chemo)therapy outcomes is challenging. Mathematical models of spheroid dynamics have the potential to enhance the informative value of experimental data, and can support study design; however, they typically face one of two limitations: while non-spatial models are computationally cheap, they lack the spatial resolution to predict oxygen-dependent radioresponse, whereas models that describe spatial cell dynamics are computationally expensive and often heavily parameterized, impeding the required calibration to experimental data. Here, we present an effectively one-dimensional mathematical model based on the cell dynamics within and across radial spheres which fully incorporates the 3D dynamics of tumor spheroids by exploiting their approximate rotational symmetry. We demonstrate that this radial-shell (RS) model reproduces experimental spheroid growth curves of several cell lines with and without radiotherapy, showing equal or better performance than published models such as 3D agent-based models. Notably, the RS model is sufficiently efficient to enable multi-parametric optimization within previously reported and/or physiologically reasonable ranges based on experimental data. Analysis of the model reveals that the characteristic change of dynamics observed in experiments at small spheroid volume originates from the spatial scale of cell interactions. Based on the calibrated parameters, we predict the spheroid volumes at which this behavior should be observable. Finally, we demonstrate how the generic parameterization of the model allows direct parameter transfer to 3D agent-based models.https://www.mdpi.com/2072-6694/15/23/5645spheroidsspatio-temporal mathematical modellingcellular automatonradial shell modelgrowth curve3D growth |
| spellingShingle | Florian Franke Soňa Michlíková Sebastian Aland Leoni A. Kunz-Schughart Anja Voss-Böhme Steffen Lange Efficient Radial-Shell Model for 3D Tumor Spheroid Dynamics with Radiotherapy Cancers spheroids spatio-temporal mathematical modelling cellular automaton radial shell model growth curve 3D growth |
| title | Efficient Radial-Shell Model for 3D Tumor Spheroid Dynamics with Radiotherapy |
| title_full | Efficient Radial-Shell Model for 3D Tumor Spheroid Dynamics with Radiotherapy |
| title_fullStr | Efficient Radial-Shell Model for 3D Tumor Spheroid Dynamics with Radiotherapy |
| title_full_unstemmed | Efficient Radial-Shell Model for 3D Tumor Spheroid Dynamics with Radiotherapy |
| title_short | Efficient Radial-Shell Model for 3D Tumor Spheroid Dynamics with Radiotherapy |
| title_sort | efficient radial shell model for 3d tumor spheroid dynamics with radiotherapy |
| topic | spheroids spatio-temporal mathematical modelling cellular automaton radial shell model growth curve 3D growth |
| url | https://www.mdpi.com/2072-6694/15/23/5645 |
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