E-Thesis 32 views 4 downloads
Modelling the spatial ecology of cancer / AMY MILNE
Swansea University Author: AMY MILNE
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Copyright: the author, Amy Milne, 2026. Distributed under the terms of a Creative Commons Attribution 4.0 License (CC BY 4.0)
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DOI (Published version): 10.23889/SUThesis.71776
Abstract
A major disadvantage in molecularly targeted therapies for cancer is the development of de novo resistance. While much focus is on cell-based mechanisms, it is known that the microenvironment also plays a crucial role.Protected by microenvironmental mechanisms, disease persists during targeted thera...
| Published: |
Swansea
2026
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| Institution: | Swansea University |
| Degree level: | Doctoral |
| Degree name: | Ph.D |
| Supervisor: | Picco, N., and Powathil, G. |
| URI: | https://cronfa.swan.ac.uk/Record/cronfa71776 |
| Abstract: |
A major disadvantage in molecularly targeted therapies for cancer is the development of de novo resistance. While much focus is on cell-based mechanisms, it is known that the microenvironment also plays a crucial role.Protected by microenvironmental mechanisms, disease persists during targeted therapy allowing for the accumulation of genetic and epigenetic modifications, eventually leading to permanent resistance and treatment failure. This thesis examines interactions between cancer cells and cancer associated fibroblasts (CAFs) to understand the local crosstalk facilitating residual disease driven by microenvironmental mechanisms, namely environmentally mediated drug resistance. Using a hybrid-discrete-continuum model, we explore how treatment-induced stress responses can elicit CAF responses and how breaks in treatment allow microenvironment normalisation as the stress response subsides. We investigate how fluctuating environmental conditions shape the local crosstalk and ultimately drive residual disease. Our experimentally calibrated model identifies environmental and treatment conditions that allow tumour eradication and those that enable survival. We find two very distinct mechanisms of resistance underpinning residual disease formed by environmental mechanisms. Finally, when we introduce cell-based mechanisms of resistance on top of environmental-driven mechanisms, we find that environmental conditions shape the phenotypic variation of residual and relapsing disease. This work provides a better understanding of the mechanisms that drive the creation of localised residual disease and disease relapse to molecularly targeted therapies. |
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| Keywords: |
Multiscale mathematical modelling, Oncology, Tumour microenvironment, Resistance |
| College: |
Faculty of Science and Engineering |
| Funders: |
EPSRC doctoral training grant |