Author:
Cox Megan C.,Mendes Rita,Silva Fernanda,Mendes Teresa F.,Zelaya-Lazo Adelyn,Halwachs Kathleen,Purkal Julie J.,Isidro Inês A.,Félix Ana,Boghaert Erwin R.,Brito Catarina
Abstract
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.
Funder
Fundação para a Ciência e a Tecnologia
AbbVie
Horizon 2020 Framework Programme
Publisher
Springer Science and Business Media LLC
Cited by
20 articles.
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