Title :

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.

Author(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]

Journal title :

Journal of Experimental & Clinical Cancer Research

Abbreviated title :

J Exp Clin Cancer Res

Volume number :

42

Pages :

260

Publication date :

2023-10-07

ISSN :

1756-9966

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [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 ...
Show more >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.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Plateformes Lilloises en Biologie et Santé (PLBS) - UAR 2014 - US 41

Submission date :

2023-12-21T06:31:58Z
2024-01-26T13:23:18Z