Spatio-temporal modelling of phenotypic heterogeneity in tumour tissues and its impact on radiotherapy treatment

DOI10.1016/J.JTBI.2022.111248zbMATH Open1504.92032arXiv2110.10105OpenAlexW3207346905WikidataQ115063351 ScholiaQ115063351MaRDI QIDQ2109231FDOQ2109231

Authors: Yanyan Li 

Publication date: 20 December 2022

Published in: Journal of Theoretical Biology (Search for Journal in Brave)

Abstract: We present a mathematical model that describes how tumour heterogeneity evolves in a tissue slice that is oxygenated by a single blood vessel. Phenotype is identified with the stemness level of a cell, $s$, that determines its proliferative capacity, apoptosis propensity and response to treatment. Our study is based on numerical bifurcation analysis and dynamical simulations of a system of coupled non-local (in phenotypic space) partial differential equations that links the phenotypic evolution of the tumour cells to local oxygen levels in the tissue. In our formulation, we consider a 1D geometry where oxygen is supplied by a blood vessel located on the domain boundary and consumed by the tumour cells as it diffuses through the tissue. For biologically relevant parameter values, the system exhibits multiple steady states; in particular, depending on the initial conditions, the tumour is either eliminated ("tumour-extinction") or it persists ("tumour-invasion"). We conclude by using the model to investigate tumour responses to radiotherapy (RT), and focus on establishing which RT strategies can eliminate the tumour. Numerical simulations reveal how phenotypic heterogeneity evolves during treatment and highlight the critical role of tissue oxygen levels on the efficacy of radiation protocols that are commonly used clinically.

Full work available at URL: https://arxiv.org/abs/2110.10105

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zbMATH Keywords

heterogeneitycancer stem cellsradio-resistance

Mathematics Subject Classification ID

Medical applications (general) (92C50) Numerical bifurcation problems (65P30) Pathology, pathophysiology (92C32)

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Cited In (14)

• The Importance of Spatial Distribution of Stemness and Proliferation State in Determining Tumor Radioresponse
• Evolutionary dynamics in vascularised tumours under chemotherapy: mathematical modelling, asymptotic analysis and numerical simulations
• Investigating the influence of growth arrest mechanisms on tumour responses to radiotherapy
• Simulated ablation for detection of cells impacting paracrine signalling in histology analysis
• Blood lipoproteins shape the phenotype and lipid content of early atherosclerotic lesion macrophages: a dual-structured mathematical model
• The role of spatial variations of abiotic factors in mediating intratumour phenotypic heterogeneity
• Mathematical modeling and quantitative analysis of phenotypic plasticity during tumor evolution based on single-cell data
• A new lipid-structured model to investigate the opposing effects of LDL and HDL on atherosclerotic plaque macrophages
• Phenotypic variation modulates the growth dynamics and response to radiotherapy of solid tumours under normoxia and hypoxia
• Modeling the emergence of phenotypic heterogeneity in vascularized tumors
• Characterising cancer cell responses to cyclic hypoxia using mathematical modelling
• Optimizing multi-modal cancer treatment under 3D spatio-temporal tumor growth
• Mathematical modelling of phenotypic selection within solid tumours
• Modeling the effects of space structure and combination therapies on phenotypic heterogeneity and drug resistance in solid tumors

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