Modelling the spatial ecology of cancer

MILNE, AMY

doi:10.23889/SUThesis.71776

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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...

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Published:	Swansea 2026
Institution:	Swansea University
Degree level:	Doctoral
Degree name:	Ph.D
Supervisor:	Picco, N., and Powathil, G.
URI:	https://cronfa.swan.ac.uk/Record/cronfa71776

first_indexed	2026-04-21T13:34:41Z
last_indexed	2026-04-22T09:44:59Z
id	cronfa71776
recordtype	RisThesis
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spelling	2026-04-21T14:56:06.8944556 v2 71776 2026-04-21 Modelling the spatial ecology of cancer 1cab987a09d7377dfc4fc713c07d3316 AMY MILNE AMY MILNE true false 2026-04-21 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. E-Thesis Swansea Multiscale mathematical modelling, Oncology, Tumour microenvironment, Resistance 16 2 2026 2026-02-16 10.23889/SUThesis.71776 COLLEGE NANME COLLEGE CODE Swansea University Picco, N., and Powathil, G. Doctoral Ph.D EPSRC doctoral training grant EPSRC doctoral training grant 2026-04-21T14:56:06.8944556 2026-04-21T14:25:44.0845366 Faculty of Science and Engineering School of Mathematics and Computer Science - Mathematics AMY MILNE 1 71776__36544__17664d75a28147d5bfe35803788c2dad.pdf 2026_Milne_A.final.71776.pdf 2026-04-21T14:33:24.3475241 Output 11952333 application/pdf E-Thesis – open access true Copyright: the author, Amy Milne, 2026. Distributed under the terms of a Creative Commons Attribution 4.0 License (CC BY 4.0) true eng https://creativecommons.org/licenses/by/4.0/
title	Modelling the spatial ecology of cancer
spellingShingle	Modelling the spatial ecology of cancer AMY MILNE
title_short	Modelling the spatial ecology of cancer
title_full	Modelling the spatial ecology of cancer
title_fullStr	Modelling the spatial ecology of cancer
title_full_unstemmed	Modelling the spatial ecology of cancer
title_sort	Modelling the spatial ecology of cancer
author_id_str_mv	1cab987a09d7377dfc4fc713c07d3316
author_id_fullname_str_mv	1cab987a09d7377dfc4fc713c07d3316_***_AMY MILNE
author	AMY MILNE
author2	AMY MILNE
format	E-Thesis
publishDate	2026
institution	Swansea University
doi_str_mv	10.23889/SUThesis.71776
college_str	Faculty of Science and Engineering
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hierarchy_top_title	Faculty of Science and Engineering
hierarchy_parent_id	facultyofscienceandengineering
hierarchy_parent_title	Faculty of Science and Engineering
department_str	School of Mathematics and Computer Science - Mathematics{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Mathematics and Computer Science - Mathematics
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description	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.
published_date	2026-02-16T10:44:59Z
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score	11.103362

Modelling the spatial ecology of cancer / AMY MILNE

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