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

Abstract The 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...

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Autores principales:	Megan C. Cox, Rita Mendes, Fernanda Silva, Teresa F. Mendes, Adelyn Zelaya-Lazo, Kathleen Halwachs, Julie J. Purkal, Inês A. Isidro, Ana Félix, Erwin R. Boghaert, Catarina Brito
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6ba6021cf4734f4ebc89722a5ae55c02
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spelling	oai:doaj.org-article:6ba6021cf4734f4ebc89722a5ae55c022021-12-02T18:02:22ZApplication of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models10.1038/s41598-021-97894-02045-2322https://doaj.org/article/6ba6021cf4734f4ebc89722a5ae55c022021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97894-0https://doaj.org/toc/2045-2322Abstract The 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.Megan C. CoxRita MendesFernanda SilvaTeresa F. MendesAdelyn Zelaya-LazoKathleen HalwachsJulie J. PurkalInês A. IsidroAna FélixErwin R. BoghaertCatarina BritoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Megan C. Cox Rita Mendes Fernanda Silva Teresa F. Mendes Adelyn Zelaya-Lazo Kathleen Halwachs Julie J. Purkal Inês A. Isidro Ana Félix Erwin R. Boghaert Catarina Brito Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models
description	Abstract The 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.
format	article
author	Megan C. Cox Rita Mendes Fernanda Silva Teresa F. Mendes Adelyn Zelaya-Lazo Kathleen Halwachs Julie J. Purkal Inês A. Isidro Ana Félix Erwin R. Boghaert Catarina Brito
author_facet	Megan C. Cox Rita Mendes Fernanda Silva Teresa F. Mendes Adelyn Zelaya-Lazo Kathleen Halwachs Julie J. Purkal Inês A. Isidro Ana Félix Erwin R. Boghaert Catarina Brito
author_sort	Megan C. Cox
title	Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models
title_short	Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models
title_full	Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models
title_fullStr	Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models
title_full_unstemmed	Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models
title_sort	application of ldh assay for therapeutic efficacy evaluation of ex vivo tumor models
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6ba6021cf4734f4ebc89722a5ae55c02
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Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models

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