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

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...

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Main Authors: Lucie Thorel, Pierre-Marie Morice, Hippolyte Paysant, Romane Florent, Guillaume Babin, Cécilia Thomine, Marion Perréard, Edwige Abeilard, Florence Giffard, Emilie Brotin, Christophe Denoyelle, Céline Villenet, Shéhérazade Sebda, Mélanie Briand, Florence Joly, Enora Dolivet, Didier Goux, Cécile Blanc-Fournier, Corinne Jeanne, Marie Villedieu, Matthieu Meryet-Figuiere, Martin Figeac, Laurent Poulain, Louis-Bastien Weiswald
Format: Article
Language:English
Published: BMC 2023-10-01
Series:Journal of Experimental & Clinical Cancer Research
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Online Access:https://doi.org/10.1186/s13046-023-02809-8
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Summary: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.
ISSN:1756-9966