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

被引：14

作者：

Thorel, Lucie ^{[1
]}

Morice, Pierre-Marie ^{[1
]}

Paysant, Hippolyte ^{[1
]}

Florent, Romane ^{[1
,2
,3
]}

Babin, Guillaume ^{[1
,4
]}

Thomine, Cecilia ^{[1
]}

Perreard, Marion ^{[1
]}

Abeilard, Edwige ^{[1
,3
]}

Giffard, Florence ^{[1
,3
]}

Brotin, Emilie ^{[5
]}

Denoyelle, Christophe ^{[1
,3
,5
]}

Villenet, Celine ^{[6
]}

Sebda, Sheherazade ^{[6
]}

Briand, Melanie ^{[1
,7
]}

Joly, Florence ^{[8
]}

Dolivet, Enora ^{[1
,4
]}

Goux, Didier ^{[9
]}

Blanc-Fournier, Cecile ^{[1
,7
,10
]}

Jeanne, Corinne ^{[10
]}

Villedieu, Marie ^{[1
]}

Meryet-Figuiere, Matthieu ^{[1
,3
]}

Figeac, Martin ^{[6
]}

Poulain, Laurent ^{[1
,2
,7
]}

Weiswald, Louis-Bastien ^{[1
,2
,3
]}

机构：

[1] Univ Caen Normandie, Interdisciplinary Res Unit Canc Prevent & Treatmen, BioTICLA Lab Precis Med Ovarian Canc, INSERM,ANTICIPE,U1086, 3 Ave Gen Harris,BP 45026, F-14076 Caen 05, France

[2] Univ Caen Normandie, Serv Unit PLATON, ORGAPRED Core Facil, Caen, France

[3] UNICANCER, Comprehens Canc Ctr Francois Baclesse, Caen, France

[4] UNICANCER, Comprehens Canc Ctr Francois Baclesse, Dept Surg, Caen, France

[5] Univ Caen Normandie, Serv Unit PLATON, ImpedanCell Core Facil, Caen, France

[6] Univ Lille, CHU Lille, CNRS, Inserm,Inst Pasteur Lille,US 41,UAR 2014, Lille, France

[7] UNICANCER, Comprehens Canc Ctr Francois Baclesse, Biol Resources Ctr OvaRessources, Caen, France

[8] UNICANCER, Comprehens Canc Ctr Francois Baclesse, Clin Res Dept, Caen, France

[9] Univ Caen Normandie, Ctr Microscopie Appliquee Biol CMAbio3, Serv Unit EMERODE, Caen, France

[10] UNICANCER, Comprehens Canc Ctr Francois Baclesse, Dept Biopathol, Caen, France

来源：

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH | 2023年 / 42卷 / 01期

关键词：

Ovarian clear cell carcinoma; Patient-derived tumor organoids; Patient-derived xenograft; Patient-derived cell lines; Precision medicine; Predictive functional assays; EXPRESSION; MUTATIONS; PROGNOSIS; CULTURE; PREDICT; MODEL;

D O I：

10.1186/s13046-023-02809-8

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：17

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