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. - Université de Lille Accéder directement au contenu
Article Dans Une Revue Journal of experimental & clinical cancer research Année : 2023

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.

P. M. Morice
  • Fonction : Auteur
H. Paysant
  • Fonction : Auteur
R. Florent
  • Fonction : Auteur
G. Babin
  • Fonction : Auteur
C. Thomine
  • Fonction : Auteur
M. Perréard
  • Fonction : Auteur
E. Abeilard
  • Fonction : Auteur
F. Giffard
  • Fonction : Auteur
E. Brotin
  • Fonction : Auteur
C. Denoyelle
  • Fonction : Auteur
M. Briand
  • Fonction : Auteur
F. Joly
  • Fonction : Auteur
E. Dolivet
  • Fonction : Auteur
D. Goux
  • Fonction : Auteur
C. Blanc-Fournier
  • Fonction : Auteur
C. Jeanne
  • Fonction : Auteur
M. Villedieu
  • Fonction : Auteur
M. Meryet-Figuiere
  • Fonction : Auteur
L. Poulain
  • Fonction : Auteur
L. B. Weiswald
  • Fonction : Auteur

Résumé

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.
Fichier principal
Vignette du fichier
s13046-023-02809-8.pdf (4.31 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-04419676 , version 1 (26-01-2024)

Identifiants

Citer

L. Thorel, P. M. Morice, H. Paysant, R. Florent, G. Babin, et al.. 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.. Journal of experimental & clinical cancer research, 2023, Journal of Experimental & Clinical Cancer Research, 42, pp.260. ⟨10.1186/s13046-023-02809-8⟩. ⟨hal-04419676⟩
14 Consultations
5 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More