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dc.contributor.authorAzharuddin, Mohammad
dc.contributor.authorRoberg, Karin
dc.contributor.authorDhara, Ashis Kumar
dc.contributor.authorJain, Mayur Vilas
dc.contributor.authorDarcy, Padraig
dc.contributor.authorHinkula, Jorma
dc.contributor.authorSlater, Nigel K H
dc.contributor.authorPatra, Hirak K
dc.date.accessioned2020-01-30T01:52:13Z
dc.date.available2020-01-30T01:52:13Z
dc.date.issued2019-12-27
dc.identifier.issn2045-2322
dc.identifier.other31882620
dc.identifier.otherPMC6934860
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/301477
dc.description.abstractOne of the hallmarks of cancers is their ability to develop resistance against therapeutic agents. Therefore, developing effective in vitro strategies to identify drug resistance remains of paramount importance for successful treatment. One of the ways cancer cells achieve drug resistance is through the expression of efflux pumps that actively pump drugs out of the cells. To date, several studies have investigated the potential of using 3-dimensional (3D) multicellular tumor spheroids (MCSs) to assess drug resistance; however, a unified system that uses MCSs to differentiate between multi drug resistance (MDR) and non-MDR cells does not yet exist. In the present report we describe MCSs obtained from post-diagnosed, pre-treated patient-derived (PTPD) cell lines from head and neck squamous cancer cells (HNSCC) that often develop resistance to therapy. We employed an integrated approach combining response to clinical drugs and screening cytotoxicity, monitoring real-time drug uptake, and assessing transporter activity using flow cytometry in the presence and absence of their respective specific inhibitors. The report shows a comparative response to MDR, drug efflux capability and reactive oxygen species (ROS) activity to assess the resistance profile of PTPD MCSs and two-dimensional (2D) monolayer cultures of the same set of cell lines. We show that MCSs provide a robust and reliable in vitro model to evaluate clinical relevance. Our proposed strategy can also be clinically applicable for profiling drug resistance in cancers with unknown resistance profiles, which consequently can indicate benefit from downstream therapy.
dc.languageeng
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2045-2322
dc.sourcenlmid: 101563288
dc.titleDissecting multi drug resistance in head and neck cancer cells using multicellular tumor spheroids.
dc.typeArticle
dc.date.updated2020-01-30T01:52:13Z
dc.identifier.doi10.17863/CAM.48549
rioxxterms.versionofrecord10.1038/s41598-019-56273-6
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidRoberg, Karin [0000-0003-1208-9746]
dc.contributor.orcidPatra, Hirak K [0000-0002-6142-5489]


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International