| Title: |
Long-term patient-derived ovarian cancer organoids closely recapitulate tumor of origin and clinical response. |
| Authors: |
Thorel, L.; Dolivet, E.; Morice, P. M.; Florent, R.; Divoux, J.; Perréard, M.; Lecouflet, L.; Desmartin, G.; Alagama, C. M.; Giffard, F.; Leconte, A.; Lequesne, J.; Clarisse, B.; Briand, M.; Traoré, Alimatou; Villenet, Celine; Meneboo, Jean-Pascal; Babin, G.; Gaichies, L.; Martin-Françoise, S.; Brun, J. L.; Rouzier, R.; Brotin, E.; Denoyelle, C.; Vigneron, N.; Leman, R.; Vaur, D.; Castera, L.; Blanc-Fournier, C.; Elie, N.; Plancoulaine, B.; Joly, F.; Meryet-Figuière, M.; Figeac, Martin; Weiswald, Louis Bastien; Poulain, Laurent |
| Contributors: |
Université de Lille; CHU Lille; CNRS; Inserm; Institut Pasteur de Lille; Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 PLBS; Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers ANTICIPE |
| Publisher Information: |
BMC |
| Publication Year: |
2025 |
| Collection: |
LillOA (Lille Open Archive - Université de Lille) |
| Description: |
Background Ovarian cancers are the second cause of death from gynecological cancers worldwide, due to a late diagnosis combined with the development of resistance to chemotherapy. However, half of these cancers present alterations in Homologous Recombination (HR), making them sensitive to inhibitors of the PARP protein (PARPi), involved in DNA repair. Nevertheless, identifying patients who respond to chemotherapy and selecting those eligible for PARPi remains a challenge for clinicians. In this context, the use of Patient-Derived Tumor Organoids (PDTO) for predictive functional testing represents an interesting prospect for clinical decision making. Methods Here we established a panel of 37 long-term PDTO models of various histological subtypes from 31 ovarian cancer patients. Histological and molecular profiles of PDTO were compared to tumor sample of origin using immunohistochemical analyses and global approaches (copy number variation and transcriptomic profiling). PDTO models were exposed to standard drugs for ovarian cancer patients, including PARPi, and response was assessed using viability assay. To further define the HR status of PDTO, we performed a functional assay evaluating the ability of PDTO to initiate HR (RECAP test) using automated histo-imaging quantitative analysis of RAD51 foci, as well as an NGS analysis based on the sequencing of an HR-related genes panel to obtain a Genome Instability Score (GIS). Results We demonstrated that PDTO mimicked histological and expression of tumor markers of paired tumors. Moreover, non-negative matrix factorization approach revealed that PDTO recapitulated the transcriptomic profile of the cancer component from their sample of origin. Screening of chemotherapeutic drugs showed that PDTO exhibit heterogeneous responses, and that response of PDTO from high-grade serous ovarian carcinoma to carboplatin recapitulated patient response to first-line treatment. Additionally, the detection of HRD phenotype of PDTO using functional assay was associated with the results ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/rdf+xml; charset=utf-8; application/octet-stream |
| Language: |
English |
| Relation: |
Journal of experimental & clinical cancer research; J Exp Clin Cancer Res |
| Availability: |
https://lilloa.univ-lille.fr/handle/20.500.12210/131520; https://hdl.handle.net/20.500.12210/131520 |
| Rights: |
Attribution 3.0 United States ; info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.6FB597BB |
| Database: |
BASE |