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In vitro patient-derived 3D mesothelioma tumor organoids facilitate patient-centric therapeutic screening

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dc.contributor.authorMazzocchi, Andrea R.en
dc.contributor.authorRajan, Shiny A. P.en
dc.contributor.authorVotanopoulos, Konstantinos I.en
dc.contributor.authorHall, Adam R.en
dc.contributor.authorSkardal, Aleksanderen
dc.contributor.departmentSchool of Biomedical Engineering and Sciencesen
dc.date.accessioned2018-12-21T14:55:34Zen
dc.date.available2018-12-21T14:55:34Zen
dc.date.issued2018-02-13en
dc.description.abstractVariability in patient response to anti-cancer drugs is currently addressed by relating genetic mutations to chemotherapy through precision medicine. However, practical benefits of precision medicine to therapy design are less clear. Even after identification of mutations, oncologists are often left with several drug options, and for some patients there is no definitive treatment solution. There is a need for model systems to help predict personalized responses to chemotherapeutics. We have microengineered 3D tumor organoids directly from fresh tumor biopsies to provide patient-specific models with which treatment optimization can be performed before initiation of therapy. We demonstrate the initial implementation of this platform using tumor biospecimens surgically removed from two mesothelioma patients. First, we show the ability to biofabricate and maintain viable 3D tumor constructs within a tumor-on-a-chip microfluidic device. Second, we demonstrate that results of on-chip chemotherapy screening mimic those observed in subjects themselves. Finally, we demonstrate mutation-specific drug testing by considering the results of precision medicine genetic screening and confirming the effectiveness of the non-standard compound 3-deazaneplanocin A for an identified mutation. This patient-derived tumor organoid strategy is adaptable to a wide variety of cancers and may provide a framework with which to improve efforts in precision medicine oncology.en
dc.description.notesAS acknowledges funds from the Wake Forest Baptist Medical Center Clinical and Translational Science Institute Open Pilot Program. ARH acknowledges start-up funds from Wake Forest University School of Medicine. AS and ARH acknowledge services from the Wake Forest Cellular Imaging Shared Resource supported by the Comprehensive Cancer Center at Wake Forest Baptist Medical Center's NCI Cancer Center Support Grant P30CA012197. AS and ARH acknowledge funding by the Defense Threat Reduction Agency (DTRA) under Space and Naval Warfare Systems Center Pacific (SSC PACIFIC) Contract No. N6601-13-C-2027. The publication of this material does not constitute approval by the government of the findings or conclusions herein. The authors gratefully acknowledge Dr. Frank Marini for access to the confocal microscopy equipment employed in the studies.en
dc.description.sponsorshipWake Forest Baptist Medical Center Clinical and Translational Science Institute Open Pilot Program; Wake Forest University School of Medicine; Comprehensive Cancer Center at Wake Forest Baptist Medical Center's NCI Cancer Center Support Grant [P30CA012197]; Defense Threat Reduction Agency (DTRA) under Space and Naval Warfare Systems Center Pacific (SSC PACIFIC) [N6601-13-C-2027]en
dc.format.extent12 pagesen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41598-018-21200-8en
dc.identifier.issn2045-2322en
dc.identifier.other2886en
dc.identifier.pmid29440675en
dc.identifier.urihttp://hdl.handle.net/10919/86490en
dc.identifier.volume8en
dc.language.isoenen
dc.publisherSpringer Natureen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectsynthetic extracellular matricesen
dc.subjectprecision cancer medicineen
dc.subjecton-a-chipen
dc.subjectdrug discoveryen
dc.subjecttissue modelsen
dc.subjectcell-cultureen
dc.subjectbap1en
dc.subjectadenocarcinomaen
dc.subjectexpressionen
dc.subjectcalretininen
dc.titleIn vitro patient-derived 3D mesothelioma tumor organoids facilitate patient-centric therapeutic screeningen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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