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.
Ovarian clear cell carcinoma
Patient-derived cell lines
Patient-derived tumor organoids
Patient-derived xenograft
Precision medicine
Predictive functional assays
Journal
Journal of experimental & clinical cancer research : CR
ISSN: 1756-9966
Titre abrégé: J Exp Clin Cancer Res
Pays: England
ID NLM: 8308647
Informations de publication
Date de publication:
07 Oct 2023
07 Oct 2023
Historique:
received:
03
03
2023
accepted:
22
08
2023
medline:
9
10
2023
pubmed:
7
10
2023
entrez:
6
10
2023
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 37803448
doi: 10.1186/s13046-023-02809-8
pii: 10.1186/s13046-023-02809-8
pmc: PMC10559504
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
260Informations de copyright
© 2023. Italian National Cancer Institute ‘Regina Elena’.
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