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dc.contributor.authorGevertz, Jana L.
dc.contributor.authorAminzare, Zahra
dc.contributor.authorNorton, Kerri-Ann
dc.contributor.authorPérez-Velázquez, Judith
dc.contributor.authorVolkening, Alexandria
dc.contributor.authorRejniak, Katarzyna A.
dc.date.accessioned2017-09-23T15:25:55Z
dc.date.available2017-09-23T15:25:55Z
dc.date.issued2015
dc.identifier.citationJ.L. Gevertz, Z. Aminzare, K. Norton, J. Pérez-Velázquez, A. Volkening and K.A. Rejniak, 2015. Emergence of anti-cancer drug resistance: Exploring the importance of the microenvironmental niche and tumor heterogeneity through a spatial model. In “Applications of Dynamical Systems in Biology and Medicine”, IMA Volumes in Mathematics and its Applications, vol 158, Springer-Verlag, A. Radunskaya and T. Jackson (Eds).en_US
dc.identifier.urihttps://dx.doi.org/10.1007/978-1-4939-2782-1_1
dc.descriptionThis is a post-peer-review, pre-copyedit version of an article published in IMA Volumes in Mathematics and its Applications. The final authenticated version is available online at: https://dx.doi.org/10.1007/978-1-4939-2782-1_1en_US
dc.description.abstractPractically, all chemotherapeutic agents lead to drug resistance. Clinically, it is a challenge to determine whether resistance arises prior to, or as a result of, cancer therapy. Further, a number of different intracellular and microenvironmental factors have been correlated with the emergence of drug resistance. With the goal of better understanding drug resistance and its connection with the tumor microenvironment, we have developed a hybrid discrete-continuous mathematical model. In this model, cancer cells described through a particle-spring approach respond to dynamically changing oxygen and DNA damaging drug concentrations described through partial differential equations. We thoroughly explored the behavior of our self-calibrated model under the following common conditions: a fixed layout of the vasculature, an identical initial configuration of cancer cells, the same mechanism of drug action, and one mechanism of cellular response to the drug. We considered one set of simulations in which drug resistance existed prior to the start of treatment, and another set in which drug resistance is acquired in response to treatment. This allows us to compare how both kinds of resistance influence the spatial and temporal dynamics of the developing tumor, and its clonal diversity. We show that both pre-existing and acquired resistance can give rise to three biologically distinct parameter regimes: successful tumor eradication, reduced effectiveness of drug during the course of treatment (resistance), and complete treatment failure. When a drug resistant tumor population forms from cells that acquire resistance, we find that the spatial component of our model (the microenvironment) has a significant impact on the transient and long-term tumor behavior. On the other hand, when a resistant tumor population forms from pre-existing resistant cells, the microenvironment only has a minimal transient impact on treatment response. Finally, we present evidence that the microenvironmental niches of low drug/sufficient oxygen and low drug/low oxygen play an important role in tumor cell survival and tumor expansion. This may play role in designing new therapeutic agents or new drug combination schedules.en_US
dc.language.isoen_USen_US
dc.publisherSpringer Verlagen_US
dc.relation.ispartofApplications of Dynamical Systems in Biology and Medicine
dc.subjectTumor therapyen_US
dc.subjectTumor environmenten_US
dc.subjectHybrid modelen_US
dc.subjectIndividual cell-based modelen_US
dc.titleEmergence of Anti-Cancer Drug Resistance: Exploring the Importance of the Microenvironmental Niche via a Spatial Modelen_US
dc.typeBook chapteren_US
dc.typeTexten_US
dc.typePostprinten_US
prism.publicationNameIMA Volumes in Mathematics and its Applicationsen_US
prism.volume158
prism.publicationDate2015
prism.startingPage1
prism.endingPage34
dc.identifier.handlehttps://dr.tcnj.edu/handle/2900/1421


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