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Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models

2021-12Artigo científico Acesso aberto
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dc.contributor.authorCox, Megan C.
dc.contributor.authorMendes, Rita
dc.contributor.authorSilva, Fernanda
dc.contributor.authorMendes, Teresa F.
dc.contributor.authorZelaya-Lazo, Adelyn
dc.contributor.authorHalwachs, Kathleen
dc.contributor.authorPurkal, Julie J.
dc.contributor.authorIsidro, Inês A.
dc.contributor.authorFélix, Ana
dc.contributor.authorBoghaert, Erwin R.
dc.contributor.authorBrito, Catarina
dc.contributor.institutionInstituto de Tecnologia Química e Biológica António Xavier (ITQB)
dc.contributor.institutionCentro de Estudos de Doenças Crónicas (CEDOC)
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.pblNature Publishing Group
dc.date.accessioned2021-10-22T03:43:07Z
dc.date.available2021-10-22T03:43:07Z
dc.date.issued2021-12
dc.descriptionFunding Information: This work was supported by AbbVie and by iNOVA4Health – UIDB/04462/2020, a program financially supported by Fundação para a Ciência e Tecnologia (FCT) / Ministério da Educação e Ciência, through national funds. RM and TFM were recipients of PhD fellowships funded by FCT (SFRH/BD/132163/2017 and PD/BD/128377/2017, respectively) and CB was funded by “The Discoveries Centre for Regenerative and Precision Medicine” (European Commission Horizon 2020 Research and Innovation programme, under the Grant Agreement 739572). Publisher Copyright: © 2021, The Author(s).
dc.description.abstractThe current standard preclinical oncology models are not able to fully recapitulate therapeutic targets and clinically relevant disease biology, evidenced by the 90% attrition rate of new therapies in clinical trials. Three-dimensional (3D) culture systems have the potential to enhance the relevance of preclinical models. However, the limitations of currently available cellular assays to accurately evaluate therapeutic efficacy in these models are hindering their widespread adoption. We assessed the compatibility of the lactate dehydrogenase (LDH) assay in 3D spheroid cultures against other commercially available readout methods. We developed a standardized protocol to apply the LDH assay to ex vivo cultures, considering the impact of culture growth dynamics. We show that accounting for growth rates and background release levels of LDH are sufficient to make the LDH assay a suitable methodology for longitudinal monitoring and endpoint assessment of therapeutic efficacy in both cell line-derived xenografts (xenospheres) and patient-derived explant cultures. This method has the added value of being non-destructive and not dependent on reagent penetration or manipulation of the parent material. The establishment of reliable readout methods for complex 3D culture systems will further the utility of these tumor models in preclinical and co-clinical drug development studies.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent2806691
dc.identifier.doi10.1038/s41598-021-97894-0
dc.identifier.issn2045-2322
dc.identifier.otherPURE: 34091209
dc.identifier.otherPURE UUID: 36db4579-a838-4c0b-929a-5a918b76da1d
dc.identifier.otherScopus: 85115116348
dc.identifier.otherORCID: /0000-0002-2653-2262/work/101864328
dc.identifier.otherPubMed: 34535719
dc.identifier.urihttp://hdl.handle.net/10362/126482
dc.identifier.urlhttps://www.scopus.com/pages/publications/85115116348
dc.language.isoeng
dc.peerreviewedyes
dc.subjectGeneral
dc.titleApplication of LDH assay for therapeutic efficacy evaluation of ex vivo tumor modelsen
dc.typejournal article
degois.publication.issue1
degois.publication.titleScientific Reports
degois.publication.volume11
dspace.entity.typePublication
rcaap.rightsopenAccess

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