2. Academic Validation
  3. 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

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

  • J Exp Clin Cancer Res. 2023 Oct 7;42(1):260. doi: 10.1186/s13046-023-02809-8.
Lucie Thorel # 1,  Pierre-Marie Morice # 1,  Hippolyte Paysant 1,  Romane Florent 1 2 3,  Guillaume Babin 1 4,  Cécilia Thomine 1,  Marion Perréard 1,  Edwige Abeilard 1 3,  Florence Giffard 1 3,  Emilie Brotin 5,  Christophe Denoyelle 1 3 5,  Céline Villenet 6,  Shéhérazade Sebda 6,  Mélanie Briand 1 7,  Florence Joly 8,  Enora Dolivet 1 4,  Didier Goux 9,  Cécile Blanc-Fournier 1 7 10,  Corinne Jeanne 10,  Marie Villedieu 1,  Matthieu Meryet-Figuiere 1 3,  Martin Figeac 6,  Laurent Poulain 11 12 13,  Louis-Bastien Weiswald 14 15 16
Affiliations

Affiliations

  • 1 Université de Caen Normandie, INSERM U1086 ANTICIPE (Interdisciplinary Research Unit for Cancers Prevention and Treatment), BioTICLA Laboratory (Precision Medicine for Ovarian Cancers), 3 Avenue du Général Harris, BP 45026, 14 076, Caen, Cedex 05, France.
  • 2 Université de Caen Normandie, Services Unit PLATON, ORGAPRED Core Facility, Caen, France.
  • 3 UNICANCER, Comprehensive Cancer Center François Baclesse, Caen, France.
  • 4 UNICANCER, Comprehensive Cancer Center Francois Baclesse, Department of Surgery, Caen, France.
  • 5 Université de Caen Normandie, Services Unit PLATON, ImpedanCell Core Facility, Caen, France.
  • 6 University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41 - UAR 2014 - PLBS, Lille, France.
  • 7 UNICANCER, Comprehensive Cancer Center Francois Baclesse, Biological Resources Center 'OvaRessources', Caen, France.
  • 8 UNICANCER, Comprehensive Cancer Center Francois Baclesse, Clinical Research Department, Caen, France.
  • 9 Université de Caen Normandie, Services Unit EMERODE, « Centre de Microscopie Appliquée À La Biologie » CMAbio3, Caen, France.
  • 10 UNICANCER, Comprehensive Cancer Center Francois Baclesse, Department of Biopathology, Caen, France.
  • 11 Université de Caen Normandie, INSERM U1086 ANTICIPE (Interdisciplinary Research Unit for Cancers Prevention and Treatment), BioTICLA Laboratory (Precision Medicine for Ovarian Cancers), 3 Avenue du Général Harris, BP 45026, 14 076, Caen, Cedex 05, France. l.poulain@baclesse.unicancer.fr.
  • 12 Université de Caen Normandie, Services Unit PLATON, ORGAPRED Core Facility, Caen, France. l.poulain@baclesse.unicancer.fr.
  • 13 UNICANCER, Comprehensive Cancer Center Francois Baclesse, Biological Resources Center 'OvaRessources', Caen, France. l.poulain@baclesse.unicancer.fr.
  • 14 Université de Caen Normandie, INSERM U1086 ANTICIPE (Interdisciplinary Research Unit for Cancers Prevention and Treatment), BioTICLA Laboratory (Precision Medicine for Ovarian Cancers), 3 Avenue du Général Harris, BP 45026, 14 076, Caen, Cedex 05, France. lb.weiswald@baclesse.unicancer.fr.
  • 15 Université de Caen Normandie, Services Unit PLATON, ORGAPRED Core Facility, Caen, France. lb.weiswald@baclesse.unicancer.fr.
  • 16 UNICANCER, Comprehensive Cancer Center François Baclesse, Caen, France. lb.weiswald@baclesse.unicancer.fr.
  • # Contributed equally.
PMID: 37803448 DOI: 10.1186/s13046-023-02809-8
Abstract

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.

Keywords

Ovarian clear cell carcinoma; Patient-derived cell lines; Patient-derived tumor organoids; Patient-derived xenograft; Precision medicine; Predictive functional assays.

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