Journal article 405 views 81 downloads
The role of environmentally mediated drug resistance in facilitating the spatial distribution of residual disease
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Philip K. Maini ,
Alexander R. A. Anderson ,
Noemi Picco
Communications Biology, Volume: 8, Issue: 1
Swansea University Authors:
Amy Milne, Noemi Picco
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© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License.
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DOI (Published version): 10.1038/s42003-025-08585-9
Abstract
The development of de novo resistance is a major disadvantage in molecularly targeted therapies. While much focus is on cell-intrinsic mechanisms, the microenvironment is also known to play a crucial role. This study examines interactions between cancer cells and cancer associated fibroblasts (CAFs)...
| Published in: | Communications Biology |
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| ISSN: | 2399-3642 |
| Published: |
Springer Science and Business Media LLC
2025
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa70117 |
| Abstract: |
The development of de novo resistance is a major disadvantage in molecularly targeted therapies. While much focus is on cell-intrinsic mechanisms, the microenvironment is also known to play a crucial role. This study examines interactions between cancer cells and cancer associated fibroblasts (CAFs) to understand the local crosstalk facilitating residual disease. Using a hybrid-discrete-continuum model, we explore how treatment-induced stress responses can elicit CAF activation and how breaks in treatment allow microenvironment normalisation. 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 distinct mechanisms that underpin residual disease: vasculature-limited drug delivery and CAF-mediated rescue. This work provides a better understanding of the mechanisms that drive the creation of localised residual disease, crucial to informing the development of more effective treatment protocols. |
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| College: |
Faculty of Science and Engineering |
| Funders: |
This work was supported by the UK Engineering and Physical Sciences Research Council (EPSRC grant number EP/W523963/1). We acknowledge the support of the Supercomputing Wales project, which is part-funded by the European Regional Development Fund (ERDF) via the Welsh Government. |
| Issue: |
1 |