Multiscale Modelling of Cancer Response to Oncolytic Viral Therapy

Talal Alzahrani, Raluca Eftimie, Dumitru Trucu (Lead / Corresponding author)

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Abstract

Oncolytic viruses (OV) are viruses that can replicate selectively within cancer cells and destroy them. While the past few decades have seen significant progress related to the use of these viruses in clinical contexts, the success of oncolytic therapies is dampened by the complex spatial tumour-OV interactions. In this work, we present a novel multiscale moving boundary modelling for the tumour-OV interactions, which is based on coupled systems of partial differential equations both at macro-scale (tissue-scale) and at micro-scale (cell-scale) that are connected through a double feedback link. At the macro-scale, we account for the coupled dynamics of uninfected cancer cells, OV-infected cancer cells, extracellular matrix (ECM) and oncolytic viruses. At the same time, at the micro scale, we focus on essential dynamics of urokinase plasminogen activator (uPA) system which is one of the important proteolytic systems responsible for the degradation of the ECM, with notable influence in cancer invasion. While sourced by the cancer cells that arrive during their macro-dynamics within the outer proliferating rim of the tumour, the uPA micro-dynamics is crucial in determining the movement of the macro-scale tumour boundary (both in terms of direction and displacement magnitude). In this investigation, we consider three scenarios for the macro-scale tumour-OV interactions. While assuming the usual context of reaction-diffusion-taxis coupled PDEs, the three macro-dynamics scenarios gradually explore the influence of the ECM taxis over the tumour - OV interaction, in the form of haptotaxis of both uninfected and infected cells populations as well as the indirect ECM taxis for the oncolytic virus. Finally, the complex tumour-OV interactions is investigated numerically through the development a new multiscale moving boundary computational framework. While further investigation is needed to validate the findings of our modelling, for the parameter regimes that we considered, our numerical simulations indicate that the viral therapy leads to control and decrease of the overall cancer expansion and in certain cases this can result even in the elimination of the tumour.
Original languageEnglish
Pages (from-to)76-95
Number of pages20
JournalMathematical Biosciences
Volume310
Early online date5 Feb 2019
DOIs
Publication statusPublished - Apr 2019

Keywords

  • Cancer modelling
  • Multiscale modelling
  • Tumour-oncolytic virus interactions

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  • Student Theses

    Multiscale Modelling of Cancer Response to Viral Therapy

    Author: Alzahrani, T. A. M., 2020

    Supervisor: Trucu, D. (Supervisor) & Lin, P. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy

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