Modeling critical dosing strategies for stromal-induced resistance to cancer therapy
Abstract Complex interactions between stromal cells, tumor cells and therapies can influence environmental factors that in turn impact anticancer treatment efficacy. Disentangling these phenomena is critical for understanding treatment response and designing effective dosing strategies. We propose a...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | npj Systems Biology and Applications |
| Online Access: | https://doi.org/10.1038/s41540-025-00495-0 |
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| _version_ | 1823861948666609664 |
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| author | Anna K. Kraut Colleen M. Garvey Carly Strelez Shannon M. Mumenthaler Jasmine Foo |
| author_facet | Anna K. Kraut Colleen M. Garvey Carly Strelez Shannon M. Mumenthaler Jasmine Foo |
| author_sort | Anna K. Kraut |
| collection | DOAJ |
| description | Abstract Complex interactions between stromal cells, tumor cells and therapies can influence environmental factors that in turn impact anticancer treatment efficacy. Disentangling these phenomena is critical for understanding treatment response and designing effective dosing strategies. We propose a mathematical model for a common tumor-stromal interaction motif where stromal cells secrete factors that promote drug resistance. We demonstrate that the presence of this interaction modulates the therapeutic dose window of efficacy and can lead to nonmonotonic treatment response. We consider combination strategies that target stromal cells and their secretome, and identify strategies that constrain drug concentrations within the efficacious window for long-term response. We explore an experimental dataset from colorectal cancer cells treated with anti-EGFR targeting therapy, cetuximab, where cancer-associated fibroblasts increase epidermal growth factor secretion under treatment. We apply our general approach to identify a critical drug concentration threshold and study effective dosing regimens for single-drug and combination therapies. |
| format | Article |
| id | doaj-art-2d07b16e741b40f887a18b6a49734000 |
| institution | Kabale University |
| issn | 2056-7189 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Systems Biology and Applications |
| spelling | doaj-art-2d07b16e741b40f887a18b6a497340002025-02-09T12:43:13ZengNature Portfolionpj Systems Biology and Applications2056-71892025-02-0111111710.1038/s41540-025-00495-0Modeling critical dosing strategies for stromal-induced resistance to cancer therapyAnna K. Kraut0Colleen M. Garvey1Carly Strelez2Shannon M. Mumenthaler3Jasmine Foo4School of Mathematics, University of Minnesota—Twin CitiesDivision of Medical Oncology, Norris Comprehensive Cancer Center, University of Southern CaliforniaDivision of Medical Oncology, Norris Comprehensive Cancer Center, University of Southern CaliforniaDivision of Medical Oncology, Norris Comprehensive Cancer Center, University of Southern CaliforniaSchool of Mathematics, University of Minnesota—Twin CitiesAbstract Complex interactions between stromal cells, tumor cells and therapies can influence environmental factors that in turn impact anticancer treatment efficacy. Disentangling these phenomena is critical for understanding treatment response and designing effective dosing strategies. We propose a mathematical model for a common tumor-stromal interaction motif where stromal cells secrete factors that promote drug resistance. We demonstrate that the presence of this interaction modulates the therapeutic dose window of efficacy and can lead to nonmonotonic treatment response. We consider combination strategies that target stromal cells and their secretome, and identify strategies that constrain drug concentrations within the efficacious window for long-term response. We explore an experimental dataset from colorectal cancer cells treated with anti-EGFR targeting therapy, cetuximab, where cancer-associated fibroblasts increase epidermal growth factor secretion under treatment. We apply our general approach to identify a critical drug concentration threshold and study effective dosing regimens for single-drug and combination therapies.https://doi.org/10.1038/s41540-025-00495-0 |
| spellingShingle | Anna K. Kraut Colleen M. Garvey Carly Strelez Shannon M. Mumenthaler Jasmine Foo Modeling critical dosing strategies for stromal-induced resistance to cancer therapy npj Systems Biology and Applications |
| title | Modeling critical dosing strategies for stromal-induced resistance to cancer therapy |
| title_full | Modeling critical dosing strategies for stromal-induced resistance to cancer therapy |
| title_fullStr | Modeling critical dosing strategies for stromal-induced resistance to cancer therapy |
| title_full_unstemmed | Modeling critical dosing strategies for stromal-induced resistance to cancer therapy |
| title_short | Modeling critical dosing strategies for stromal-induced resistance to cancer therapy |
| title_sort | modeling critical dosing strategies for stromal induced resistance to cancer therapy |
| url | https://doi.org/10.1038/s41540-025-00495-0 |
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