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

TL;DR

This paper develops a mathematical model to understand how tumour heterogeneity evolves in oxygenated tissue and how this impacts the effectiveness of radiotherapy treatments, emphasizing the role of oxygen levels.

Contribution

It introduces a coupled PDE model linking phenotypic evolution and oxygen dynamics, providing insights into tumour persistence and treatment response.

Findings

Tumour fate depends on initial conditions and oxygen levels.

Multiple steady states exist, including tumour extinction and invasion.

Oxygen levels critically influence radiotherapy efficacy.

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.