Limiting the development of anti-cancer drug resistance in a spatial model of micrometastases
While chemoresistance in primary tumors is well-studied, much less is known about the influence of systemic chemotherapy on the development of drug resistance at metastatic sites. In this work, we use a hybrid spatial model of tumor response to a DNA damaging drug to study how the development of che...
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| Format: | Article |
| Language: | English |
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AIMS Press
2016-07-01
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| Series: | Mathematical Biosciences and Engineering |
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| Online Access: | https://www.aimspress.com/article/doi/10.3934/mbe.2016038 |
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| author | Ami B. Shah Katarzyna A. Rejniak Jana L. Gevertz |
| author_facet | Ami B. Shah Katarzyna A. Rejniak Jana L. Gevertz |
| author_sort | Ami B. Shah |
| collection | DOAJ |
| description | While chemoresistance in primary tumors is well-studied, much less is known about the influence of systemic chemotherapy on the development of drug resistance at metastatic sites. In this work, we use a hybrid spatial model of tumor response to a DNA damaging drug to study how the development of chemoresistance in micrometastases depends on the drug dosing schedule. We separately consider cell populations that harbor pre-existing resistance to the drug, and those that acquire resistance during the course of treatment. For each of these independent scenarios, we consider one hypothetical cell line that is responsive to metronomic chemotherapy, and another that with high probability cannot be eradicated by a metronomic protocol. Motivated by experimental work on ovarian cancer xenografts, we consider all possible combinations of a one week treatment protocol, repeated for three weeks, and constrained by the total weekly drug dose. Simulations reveal a small number of fractionated-dose protocols that are at least as effective as metronomic therapy in eradicating micrometastases with acquired resistance (weak or strong), while also being at least as effective on those that harbor weakly pre-existing resistant cells. Given the responsiveness of very different theoretical cell lines to these few fractionated-dose protocols, these may represent more effective ways to schedule chemotherapy with the goal of limiting metastatic tumor progression. |
| format | Article |
| id | doaj-art-ea30dd332c364f37ad29ffd6ba16b524 |
| institution | Kabale University |
| issn | 1551-0018 |
| language | English |
| publishDate | 2016-07-01 |
| publisher | AIMS Press |
| record_format | Article |
| series | Mathematical Biosciences and Engineering |
| spelling | doaj-art-ea30dd332c364f37ad29ffd6ba16b5242025-01-24T02:37:49ZengAIMS PressMathematical Biosciences and Engineering1551-00182016-07-011361185120610.3934/mbe.2016038Limiting the development of anti-cancer drug resistance in a spatial model of micrometastasesAmi B. Shah0Katarzyna A. Rejniak1Jana L. Gevertz2Department of Biology, The College of New Jersey, Ewing, NJIntegrated Mathematical Oncology Department and Center of Excellence in Cancer Imaging and Technology, H. Lee Mott Cancer Center and Research Institute, Department of Oncologic Sciences, University of South Florida, Tampa, FLDepartment of Mathematics and Statistics, The College of New Jersey, Ewing, NJWhile chemoresistance in primary tumors is well-studied, much less is known about the influence of systemic chemotherapy on the development of drug resistance at metastatic sites. In this work, we use a hybrid spatial model of tumor response to a DNA damaging drug to study how the development of chemoresistance in micrometastases depends on the drug dosing schedule. We separately consider cell populations that harbor pre-existing resistance to the drug, and those that acquire resistance during the course of treatment. For each of these independent scenarios, we consider one hypothetical cell line that is responsive to metronomic chemotherapy, and another that with high probability cannot be eradicated by a metronomic protocol. Motivated by experimental work on ovarian cancer xenografts, we consider all possible combinations of a one week treatment protocol, repeated for three weeks, and constrained by the total weekly drug dose. Simulations reveal a small number of fractionated-dose protocols that are at least as effective as metronomic therapy in eradicating micrometastases with acquired resistance (weak or strong), while also being at least as effective on those that harbor weakly pre-existing resistant cells. Given the responsiveness of very different theoretical cell lines to these few fractionated-dose protocols, these may represent more effective ways to schedule chemotherapy with the goal of limiting metastatic tumor progression.https://www.aimspress.com/article/doi/10.3934/mbe.2016038chemoresistancemetronomic chemotherapyfractionated therapymaximum tolerated dosemicrometastaseshybrid model. |
| spellingShingle | Ami B. Shah Katarzyna A. Rejniak Jana L. Gevertz Limiting the development of anti-cancer drug resistance in a spatial model of micrometastases Mathematical Biosciences and Engineering chemoresistance metronomic chemotherapy fractionated therapy maximum tolerated dose micrometastases hybrid model. |
| title | Limiting the development of anti-cancer drug resistance in a spatial model of micrometastases |
| title_full | Limiting the development of anti-cancer drug resistance in a spatial model of micrometastases |
| title_fullStr | Limiting the development of anti-cancer drug resistance in a spatial model of micrometastases |
| title_full_unstemmed | Limiting the development of anti-cancer drug resistance in a spatial model of micrometastases |
| title_short | Limiting the development of anti-cancer drug resistance in a spatial model of micrometastases |
| title_sort | limiting the development of anti cancer drug resistance in a spatial model of micrometastases |
| topic | chemoresistance metronomic chemotherapy fractionated therapy maximum tolerated dose micrometastases hybrid model. |
| url | https://www.aimspress.com/article/doi/10.3934/mbe.2016038 |
| work_keys_str_mv | AT amibshah limitingthedevelopmentofanticancerdrugresistanceinaspatialmodelofmicrometastases AT katarzynaarejniak limitingthedevelopmentofanticancerdrugresistanceinaspatialmodelofmicrometastases AT janalgevertz limitingthedevelopmentofanticancerdrugresistanceinaspatialmodelofmicrometastases |