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dc.contributor.authorBUSSCHOTS, STEVENen
dc.date.accessioned2016-01-07T15:43:17Z
dc.date.available2016-01-07T15:43:17Z
dc.date.issued2014en
dc.date.submitted2014en
dc.identifier.citationMcDermott M, Eustace AJ, Busschots S, Breen L, Crown J, Clynes M, O'Donovan N, Stordal B, In vitro Development of Chemotherapy and Targeted Therapy Drug-Resistant Cancer Cell Lines: A Practical Guide with Case Studies., Frontiers in oncology, 4, 2014, 40en
dc.identifier.issn2234-943Xen
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/75501
dc.descriptionPUBLISHEDen
dc.description.abstractThe development of a drug-resistant cell line can take from 3 to 18 months. However, little is published on the methodology of this development process. This article will discuss key decisions to be made prior to starting resistant cell line development; the choice of parent cell line, dose of selecting agent, treatment interval, and optimizing the dose of drug for the parent cell line. Clinically relevant drug-resistant cell lines are developed by mimicking the conditions cancer patients experience during chemotherapy and cell lines display between two- and eight-fold resistance compared to their parental cell line. Doses of drug administered are low, and a pulsed treatment strategy is often used where the cells recover in drug-free media. High-level laboratory models are developed with the aim of understanding potential mechanisms of resistance to chemotherapy agents. Doses of drug are higher and escalated over time. It is common to have difficulty developing stable clinically relevant drug-resistant cell lines. A comparative selection strategy of multiple cell lines or multiple chemotherapeutic agents mitigates this risk and gives insight into which agents or type of cell line develops resistance easily. Successful selection strategies from our research are presented. Pulsed-selection produced platinum or taxane-resistant large cell lung cancer (H1299 and H460) and temozolomide-resistant melanoma (Malme-3M and HT144) cell lines. Continuous selection produced a lapatinib-resistant breast cancer cell line (HCC1954). Techniques for maintaining drug-resistant cell lines are outlined including; maintaining cells with chemotherapy, pulse treating with chemotherapy, or returning to master drug-resistant stocks. The heterogeneity of drug-resistant models produced from the same parent cell line with the same chemotherapy agent is explored with reference to P-glycoprotein. Heterogeneity in drug-resistant cell lines reflects the heterogeneity that can occur in clinical drug resistance.en
dc.format.extent40en
dc.relation.ispartofseriesFrontiers in oncologyen
dc.relation.ispartofseries4en
dc.rightsYen
dc.subjectdrug-resistant cell lineen
dc.titleIn vitro Development of Chemotherapy and Targeted Therapy Drug-Resistant Cancer Cell Lines: A Practical Guide with Case Studies.en
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/busschosen
dc.identifier.rssinternalid109667en
dc.identifier.doihttp://dx.doi.org/10.3389/fonc.2014.00040en
dc.rights.ecaccessrightsopenAccess


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