Non-Local Multiscale Mathematical Modelling and Numerical Approaches for Tumour-Oncolytic Viruses Interactions

  • Abdulhamed Alsisi

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

Oncolytic virus (OV) is a potential therapeutic cancer treatment since it has the ability to selectively infect and reproduce inside cancer cells, killing them while posing no threat to healthy cells. The ability of viruses to destroy cancer cells has been known for almost a century, but the specific processes behind tumour-virus interactions have only just begun to be appreciated. Due to the rapid viral replication rate, infected cancer cells come loose, releasing infectious viral particles into the environment that can infect new cancer cells. In this work, we present a new non-local multiscale moving boundary model for the spatio-temporal cancer-OV interactions. This model investigates a crucial double feedback loop that combines the macro-scale dynamics of cancer-virus interactions with the micro-scale dynamics of proteolytic activity at the tumour interface. We explore the non-local cancer cell-cell and cell-matrix interactions, while assuming local cell-virus interactions. We examine several cancer treatment scenarios with oncolytic viruses numerically, such as the effect of injecting the OV inside the tumour, or outside it. We also look into the impact of varied cell-cell and cell-matrix contact strengths on the success of OV spreading throughout the tumour, as well as the impact of constant or density-dependent virus diffusion coefficients. Furthermore, as scientific evidence for the involvement of the go or grow hypothesis in cancer invasion grows, we continue our research by examining multiple scenarios for the complicated dynamics of the go or grow hypothesis in the presence of tumour-OV interactions. The spatio-temporal model focuses on two cancer cell types that can either be infected with the OV or maintain uninfected, and can either migrate in response to extracellular matrix (ECM) density or proliferate. We investigate the impact of transition rates between moving and growing cancer cell subpopulations, as well as the impact of viral infection and replication rates on overall tumour dynamics. Moreover, ECM components are extensively explored by cancer cells during invasion, and the distinctive contribution of ECM fibrous protein components, such as collagen and fibronectin, which play a major role in cell proliferation and migration, is of particular interest in this context. To that end, we develop our model to investigate this interaction in fibrous ECM, by dividing the ECM into two subpopulations fibrous ECM and non-fibre ECM to study the fibre aspect in cancer-ECM-OV interactions. We investigated two approaches for cell directed movement of infected cancer cells local and non-local, and the role of cross adhesion strength on cancer-OV interaction between infected and uninfected cancer cells.
Date of Award2022
Original languageEnglish
SponsorsSaudi Arabian Cultural Bureau
SupervisorDumitru Trucu (Supervisor) & Raluca Eftimie (Supervisor)

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