Carboplatin response in preclinical models for ovarian cancer: comparison of 2D monolayers, spheroids, ex vivo tumors and in vivo models

Abstract Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Among the key challenges in developing effective therapeutics is the poor translation of preclinical models used in the drug discovery pipeline. This leaves drug attrition rates and costs at an unacceptably high level....

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Autores principales:	Melica Nourmoussavi Brodeur, Kayla Simeone, Kim Leclerc-Deslauniers, Hubert Fleury, Euridice Carmona, Diane M. Provencher, Anne-Marie Mes-Masson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8cf5cb2dcdec424aabc6b0c6535c4a57
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spelling	oai:doaj.org-article:8cf5cb2dcdec424aabc6b0c6535c4a572021-12-02T18:34:01ZCarboplatin response in preclinical models for ovarian cancer: comparison of 2D monolayers, spheroids, ex vivo tumors and in vivo models10.1038/s41598-021-97434-w2045-2322https://doaj.org/article/8cf5cb2dcdec424aabc6b0c6535c4a572021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97434-whttps://doaj.org/toc/2045-2322Abstract Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Among the key challenges in developing effective therapeutics is the poor translation of preclinical models used in the drug discovery pipeline. This leaves drug attrition rates and costs at an unacceptably high level. Previous work has highlighted the discrepancies in therapeutic response between current in vitro and in vivo models. To address this, we conducted a comparison study to differentiate the carboplatin chemotherapy response across four different model systems including 2D monolayers, 3D spheroids, 3D ex vivo tumors and mouse xenograft models. We used six previously characterized EOC cell lines of varying chemosensitivity and performed viability assays for each model. In vivo results from the mouse model correlated with 2D response in 3/6 cell lines while they correlated with 3D spheroids and the ex vivo model in 4/6 and 5/5 cell lines, respectively. Our results emphasize the variability in therapeutic response across models and demonstrate that the carboplatin response in EOC cell lines cultured in a 3D ex vivo model correlates best with the in vivo response. These results highlight a more feasible, reliable, and cost-effective preclinical model with the highest translational potential for drug screening and prediction studies in EOC.Melica Nourmoussavi BrodeurKayla SimeoneKim Leclerc-DeslauniersHubert FleuryEuridice CarmonaDiane M. ProvencherAnne-Marie Mes-MassonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Melica Nourmoussavi Brodeur Kayla Simeone Kim Leclerc-Deslauniers Hubert Fleury Euridice Carmona Diane M. Provencher Anne-Marie Mes-Masson Carboplatin response in preclinical models for ovarian cancer: comparison of 2D monolayers, spheroids, ex vivo tumors and in vivo models
description	Abstract Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Among the key challenges in developing effective therapeutics is the poor translation of preclinical models used in the drug discovery pipeline. This leaves drug attrition rates and costs at an unacceptably high level. Previous work has highlighted the discrepancies in therapeutic response between current in vitro and in vivo models. To address this, we conducted a comparison study to differentiate the carboplatin chemotherapy response across four different model systems including 2D monolayers, 3D spheroids, 3D ex vivo tumors and mouse xenograft models. We used six previously characterized EOC cell lines of varying chemosensitivity and performed viability assays for each model. In vivo results from the mouse model correlated with 2D response in 3/6 cell lines while they correlated with 3D spheroids and the ex vivo model in 4/6 and 5/5 cell lines, respectively. Our results emphasize the variability in therapeutic response across models and demonstrate that the carboplatin response in EOC cell lines cultured in a 3D ex vivo model correlates best with the in vivo response. These results highlight a more feasible, reliable, and cost-effective preclinical model with the highest translational potential for drug screening and prediction studies in EOC.
format	article
author	Melica Nourmoussavi Brodeur Kayla Simeone Kim Leclerc-Deslauniers Hubert Fleury Euridice Carmona Diane M. Provencher Anne-Marie Mes-Masson
author_facet	Melica Nourmoussavi Brodeur Kayla Simeone Kim Leclerc-Deslauniers Hubert Fleury Euridice Carmona Diane M. Provencher Anne-Marie Mes-Masson
author_sort	Melica Nourmoussavi Brodeur
title	Carboplatin response in preclinical models for ovarian cancer: comparison of 2D monolayers, spheroids, ex vivo tumors and in vivo models
title_short	Carboplatin response in preclinical models for ovarian cancer: comparison of 2D monolayers, spheroids, ex vivo tumors and in vivo models
title_full	Carboplatin response in preclinical models for ovarian cancer: comparison of 2D monolayers, spheroids, ex vivo tumors and in vivo models
title_fullStr	Carboplatin response in preclinical models for ovarian cancer: comparison of 2D monolayers, spheroids, ex vivo tumors and in vivo models
title_full_unstemmed	Carboplatin response in preclinical models for ovarian cancer: comparison of 2D monolayers, spheroids, ex vivo tumors and in vivo models
title_sort	carboplatin response in preclinical models for ovarian cancer: comparison of 2d monolayers, spheroids, ex vivo tumors and in vivo models
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8cf5cb2dcdec424aabc6b0c6535c4a57
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Carboplatin response in preclinical models for ovarian cancer: comparison of 2D monolayers, spheroids, ex vivo tumors and in vivo models

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