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dc.contributor.authorShah, Ami B.
dc.contributor.authorRejniak, Katarzyna A.
dc.contributor.authorGevertz, Jana L.
dc.date.accessioned2017-09-14T18:42:55Z
dc.date.available2017-09-14T18:42:55Z
dc.date.issued2016-12
dc.identifier.citationB. Shah, Ami & Rejniak, Katarzyna & L. Gevertz, Jana. (2016). Limiting the Development of Anti-Cancer Drug Resistance in a Spatial Model of Micrometastases. Mathematical Biosciences and Engineering. 13:6. 1185-1206.en_US
dc.identifier.urihttp://dx.doi.org/10.3934/mbe.2016038
dc.description.abstractWhile 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.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Academy of Mathematical Sciencesen_US
dc.subjectMaximum tolerated doseen_US
dc.subjectMetronomic chemotherapyen_US
dc.subjectFractionated therapyen_US
dc.subjectChemoresistanceen_US
dc.subjectMicrometastasesen_US
dc.subjectHybrid modelen_US
dc.titleLimiting the development of anti-cancer drug resistance in a spatial model of micrometastasesen_US
dc.typeArticleen_US
dc.typeTexten_US
dc.typePostprinten_US
prism.publicationNameMathematical Biosciences and Engineeringen_US
prism.volume13
prism.issueIdentifier6
prism.startingPage1185
prism.endingPage1206
dc.identifier.handlehttps://dr.tcnj.edu/handle/2900/1397


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