Multiscale moving boundary modelling of cancer interactions with a fusogenic oncolytic virus: The impact of syncytia dynamics

Abstract

Oncolytic viral therapies is one of the new promising strategies against cancer, due to the ability of oncolytic viruses to specifically replicate inside cancer cells and kill them. There is increasing evidence that a sub-class of viruses that contain fusion proteins (triggering the formation of syncytia) can lead to better oncolytic results. Since the details of the tumour dynamics following syncytia formation are not fully understood, in this study we consider a modelling and computational approach to describe the effect of a fusogenic oncolytic virus on the multiscale dynamics of a spreading tumour. We show that for the baseline parameter values considered here, small syncytia diffusion coefficient leads to tumour reduction. Further tumour reduction can be obtained when we increase the probability of syncytia formation, in the context of different viral burst rates and death rates for individually-infected tumour cells and syncytia structures. Finally, we show that the type of syncytia diffusion coefficient (i.e., constant or density dependent) also impacts the outcome of the oncolytic viral therapy.

A level-set approach for a multi-scale cancer invasion model

“…Using the scale separation, we explore the micro-dynamics within a cell-scale neighbourhood of each of the boundary points x ∈ ∂Ω(t) (i.e., at each point of the macroscopic interface) that is enabled by acorresponding εY micro-domain centred at x. In brief, adopting here a multiscale modelling perspective similar to the one proposed in [4,5,6,71,52,62,63,64,65,67,72,73], the coupling of two-scale dynamics of cancer invasion is captured as follows:…”

“…In this work we present a new formulation of the link that connects the two scales of the tumour dynamics that was considered in the initial multiscale moving boundary modelling approach presented in [73] as well as in the multiscale cancer invasion modelling developments that followed [4,5,6,71,52,62,63,64,65,67,72]. In particular, the movement of the tumor boundary is here defined by a velocity field instead of a displacement of the interface.…”

Non-local multiscale approaches for tumour-oncolytic viruses interactions

“…The last two decades have seen the development of various mathematical models for multiscale cancer dynamics [1,34,39,48,49,50]. Nevertheless, there are not many multiscale mathematical models for oncolytic viral therapies and tumour-viral interactions; among the very few multiscale models we mention those in [3,4,37,38]. These models focus on local cancer cell dynamics and local interactions between cells, ECM and viruses.…”

“…In this study we develop further the multi-scale approach for modelling cancer-OV interactions introduced in [3,4], and consider non-local cell-cell and cell-matrix interactions for cancer dynamics. We are particularly interested in investigating the role of cell-cell and cell-matrix adhesion on cancer cell movement and degradation of ECM -since this further impacts the spread of OVs.…”

Numerical simulation for a class of predator–prey system with homogeneous Neumann boundary condition based on a sinc function interpolation method

“…When studying the spatial distribution structure and maintaining biodiversity [6,7] of predators and prey populations, the reaction diffusion system [8][9][10][11][12][13] can more accurately describe the interaction between predators and preys. In the PPS, spatial diffusion is reflected in the predator's efforts to catch up with the prey, and the prey's efforts to escape the predator's pursuit.…”