Comparative analysis of response to ...
Type de document :
Article dans une revue scientifique: Article original
PMID :
URL permanente :
Titre :
Comparative analysis of response to treatments and molecular features of tumor-derived organoids versus cell lines and PDX derived from the same ovarian clear cell carcinoma.
Auteur(s) :
Thorel, L. [Auteur]
Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers [ANTICIPE]
Morice, P. M. [Auteur]
Paysant, H. [Auteur]
Florent, R. [Auteur]
Babin, G. [Auteur]
Thomine, C. [Auteur]
Perréard, M. [Auteur]
Abeilard, E. [Auteur]
Giffard, F. [Auteur]
Brotin, E. [Auteur]
Denoyelle, C. [Auteur]
Villenet, Celine [Auteur]
Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS]
Genomic @ Lille - PLBS [GO@L]
Sebda, Shéhérazade [Auteur]
Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS]
Genomic @ Lille - PLBS [GO@L]
Briand, M. [Auteur]
Joly, F. [Auteur]
Dolivet, E. [Auteur]
Goux, D. [Auteur]
Blanc-Fournier, C. [Auteur]
Jeanne, C. [Auteur]
Villedieu, M. [Auteur]
Meryet-Figuiere, M. [Auteur]
Figeac, Martin [Auteur]
Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS]
Genomic @ Lille - PLBS [GO@L]
Genomic @ Lille - PLBS [GO@L]
Poulain, L. [Auteur]
Weiswald, L. B. [Auteur]
Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers [ANTICIPE]
Morice, P. M. [Auteur]
Paysant, H. [Auteur]
Florent, R. [Auteur]
Babin, G. [Auteur]
Thomine, C. [Auteur]
Perréard, M. [Auteur]
Abeilard, E. [Auteur]
Giffard, F. [Auteur]
Brotin, E. [Auteur]
Denoyelle, C. [Auteur]
Villenet, Celine [Auteur]
Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS]
Genomic @ Lille - PLBS [GO@L]
Sebda, Shéhérazade [Auteur]
Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS]
Genomic @ Lille - PLBS [GO@L]
Briand, M. [Auteur]
Joly, F. [Auteur]
Dolivet, E. [Auteur]
Goux, D. [Auteur]
Blanc-Fournier, C. [Auteur]
Jeanne, C. [Auteur]
Villedieu, M. [Auteur]
Meryet-Figuiere, M. [Auteur]
Figeac, Martin [Auteur]
Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS]
Genomic @ Lille - PLBS [GO@L]
Genomic @ Lille - PLBS [GO@L]
Poulain, L. [Auteur]
Weiswald, L. B. [Auteur]
Titre de la revue :
Journal of Experimental & Clinical Cancer Research
Nom court de la revue :
J Exp Clin Cancer Res
Numéro :
42
Pagination :
260
Date de publication :
2023-10-07
ISSN :
1756-9966
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
Background
In the era of personalized medicine, the establishment of preclinical models of cancer that faithfully recapitulate original tumors is essential to potentially guide clinical decisions.
Methods
We ...
Lire la suite >Background In the era of personalized medicine, the establishment of preclinical models of cancer that faithfully recapitulate original tumors is essential to potentially guide clinical decisions. Methods We established 7 models [4 cell lines, 2 Patient-Derived Tumor Organoids (PDTO) and 1 Patient-Derived Xenograft (PDX)], all derived from the same Ovarian Clear Cell Carcinoma (OCCC). To determine the relevance of each of these models, comprehensive characterization was performed based on morphological, histological, and transcriptomic analyses as well as on the evaluation of their response to the treatments received by the patient. These results were compared to the clinical data. Results Only the PDX and PDTO models derived from the patient tumor were able to recapitulate the patient tumor heterogeneity. The patient was refractory to carboplatin, doxorubicin and gemcitabine, while tumor cell lines were sensitive to these treatments. In contrast, PDX and PDTO models displayed resistance to the 3 drugs. The transcriptomic analysis was consistent with these results since the models recapitulating faithfully the clinical response grouped together away from the other classical 2D cell culture models. We next investigated the potential of drugs that have not been used in the patient clinical management and we identified the HDAC inhibitor belinostat as a potential effective treatment based on PDTO response. Conclusions PDX and PDTO appear to be the most relevant models, but only PDTO seem to present all the necessary prerequisites for predictive purposes and could constitute relevant tools for therapeutic decision support in the context of these particularly aggressive cancers refractory to conventional treatments.Lire moins >
Lire la suite >Background In the era of personalized medicine, the establishment of preclinical models of cancer that faithfully recapitulate original tumors is essential to potentially guide clinical decisions. Methods We established 7 models [4 cell lines, 2 Patient-Derived Tumor Organoids (PDTO) and 1 Patient-Derived Xenograft (PDX)], all derived from the same Ovarian Clear Cell Carcinoma (OCCC). To determine the relevance of each of these models, comprehensive characterization was performed based on morphological, histological, and transcriptomic analyses as well as on the evaluation of their response to the treatments received by the patient. These results were compared to the clinical data. Results Only the PDX and PDTO models derived from the patient tumor were able to recapitulate the patient tumor heterogeneity. The patient was refractory to carboplatin, doxorubicin and gemcitabine, while tumor cell lines were sensitive to these treatments. In contrast, PDX and PDTO models displayed resistance to the 3 drugs. The transcriptomic analysis was consistent with these results since the models recapitulating faithfully the clinical response grouped together away from the other classical 2D cell culture models. We next investigated the potential of drugs that have not been used in the patient clinical management and we identified the HDAC inhibitor belinostat as a potential effective treatment based on PDTO response. Conclusions PDX and PDTO appear to be the most relevant models, but only PDTO seem to present all the necessary prerequisites for predictive purposes and could constitute relevant tools for therapeutic decision support in the context of these particularly aggressive cancers refractory to conventional treatments.Lire moins >
Langue :
Anglais
Comité de lecture :
Oui
Audience :
Internationale
Vulgarisation :
Non
Date de dépôt :
2023-12-21T06:31:58Z
2024-01-26T13:23:18Z
2024-01-26T13:23:18Z
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