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. 2024 Jun 7;24(1):701.
doi: 10.1186/s12885-024-12429-w.

The OVAREX study: Establishment of ex vivo ovarian cancer models to validate innovative therapies and to identify predictive biomarkers

Lucie Thorel  1   2 , Jordane Divoux  1   2   3 , Justine Lequesne  4 , Guillaume Babin  1   5 , Pierre-Marie Morice  1   2 , Romane Florent  1   2   3 , Guillaume Desmartin  2   3 , Lucie Lecouflet  2   3 , Chloé Marde Alagama  1 , Alexandra Leconte  4 , Bénédicte Clarisse  4 , Mélanie Briand  1   6 , Roman Rouzier  5 , Léopold Gaichies  5 , Sandrine Martin-Françoise  5 , Jean-François Le Brun  5 , Christophe Denoyelle  1   2 , Nicolas Vigneron  1   2   7 , Corinne Jeanne  8 , Cécile Blanc-Fournier  1   6   8 , Raphaël Leman  9 , Dominique Vaur  9 , Martin Figeac  10 , Matthieu Meryet-Figuiere  1   2 , Florence Joly  4 , Louis-Bastien Weiswald  11   12   13 , Laurent Poulain #  14   15   16 , Enora Dolivet #  17   18
Affiliations

The OVAREX study: Establishment of ex vivo ovarian cancer models to validate innovative therapies and to identify predictive biomarkers

Lucie Thorel et al. BMC Cancer. .

Abstract

Background: Ovarian cancer is the first cause of death from gynecological malignancies mainly due to development of chemoresistance. Despite the emergence of PARP inhibitors, which have revolutionized the therapeutic management of some of these ovarian cancers, the 5-year overall survival rate remains around 45%. Therefore, it is crucial to develop new therapeutic strategies, to identify predictive biomarkers and to predict the response to treatments. In this context, functional assays based on patient-derived tumor models could constitute helpful and relevant tools for identifying efficient therapies or to guide clinical decision making.

Method: The OVAREX study is a single-center non-interventional study which aims at investigating the feasibility of establishing in vivo and ex vivo models and testing ex vivo models to predict clinical response of ovarian cancer patients. Patient-Derived Xenografts (PDX) will be established from tumor fragments engrafted subcutaneously into immunocompromised mice. Explants will be generated by slicing tumor tissues and Ascites-Derived Spheroids (ADS) will be isolated following filtration of ascites. Patient-derived tumor organoids (PDTO) will be established after dissociation of tumor tissues or ADS, cell embedding into extracellular matrix and culture in specific medium. Molecular and histological characterizations will be performed to compare tumor of origin and paired models. Response of ex vivo tumor-derived models to conventional chemotherapy and PARP inhibitors will be assessed and compared to results of companion diagnostic test and/or to the patient's response to evaluate their predictive value.

Discussion: This clinical study aims at generating PDX and ex vivo models (PDTO, ADS, and explants) from tumors or ascites of ovarian cancer patients who will undergo surgical procedure or paracentesis. We aim at demonstrating the predictive value of ex vivo models for their potential use in routine clinical practice as part of precision medicine, as well as establishing a collection of relevant ovarian cancer models that will be useful for the evaluation of future innovative therapies.

Trial registration: The clinical trial has been validated by local research ethic committee on January 25th 2019 and registered at ClinicalTrials.gov with the identifier NCT03831230 on January 28th 2019, last amendment v4 accepted on July 18, 2023.

Keywords: Explants; Ovarian cancer; Patient-derived tumor organoids; Patient-derived tumor xenografts; Predictive functional assays.; Spheroids.

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Conflict of interest statement

The authors declare no competing interests.

Figures

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Fig. 1
OVAREX study design (created with Biorender.com)
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