Spatio-temporal modelling of phenotypic heterogeneity in tumour tissues and its impact on radiotherapy treatment
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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, , 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.
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- Modeling the effects of space structure and combination therapies on phenotypic heterogeneity and drug resistance in solid tumors
- Modeling the emergence of phenotypic heterogeneity in vascularized tumors
- Mathematical modeling and quantitative analysis of phenotypic plasticity during tumor evolution based on single-cell data
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- Evolutionary dynamics in vascularised tumours under chemotherapy: mathematical modelling, asymptotic analysis and numerical simulations
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- Characterising cancer cell responses to cyclic hypoxia using mathematical modelling
- Mathematical modelling of phenotypic selection within solid tumours
- The Importance of Spatial Distribution of Stemness and Proliferation State in Determining Tumor Radioresponse
- The role of spatial variations of abiotic factors in mediating intratumour phenotypic heterogeneity
- Phenotypic variation modulates the growth dynamics and response to radiotherapy of solid tumours under normoxia and hypoxia
- Investigating the influence of growth arrest mechanisms on tumour responses to radiotherapy
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