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Observational Study
. 2023 Sep 19;23(1):883.
doi: 10.1186/s12885-023-11362-8.

The TRIPLEX study: use of patient-derived tumor organoids as an innovative tool for precision medicine in triple-negative breast cancer

Jordane Divoux  1   2   3 , Romane Florent  1   2   3 , Margaux Jacobs  4 , Justine Lequesne  5 , Jean-Michel Grellard  5 , Chankannira San  5 , Sara Grossi  5 , Katia Kerdja  5 , Bénédicte Clarisse  5 , Gwenaelle Boudier  5 , François Cherifi  4 , Mélanie Briand  1   6 , Enora Dolivet  1   7 , Alisson Johnson  4   5 , Brice Dubois  8 , Valentin Harter  8 , Joëlle Lacroix  9 , Charlotte Raboutet  9 , Brigitte Marie  9 , Nathalie Rousseau  2   10 , Cécile Blanc-Fournier  1   6   10   11 , Dominique Vaur  12 , Martin Figeac  13 , Laurent Poulain  1   3   6 , Louis-Bastien Weiswald #  14   15   16   17 , George Emile #  18   19   20
Affiliations
Observational Study

The TRIPLEX study: use of patient-derived tumor organoids as an innovative tool for precision medicine in triple-negative breast cancer

Jordane Divoux et al. BMC Cancer. .

Abstract

Background: Triple negative breast cancers (TNBC) account for approximately 15% of all breast cancers and are associated with a shorter median survival mainly due to locally advanced tumor and high risk of metastasis. The current neoadjuvant treatment for TNBC consists of a regimen of immune checkpoint blocker and chemotherapy (chemo-ICB). Despite the frequent use of this combination for TNBC treatment, moderate results are observed and its clinical benefit in TNBC remains difficult to predict. Patient-derived tumor organoids (PDTO) are 3D in vitro cellular structures obtained from patient's tumor samples. More and more evidence suggest that these models could predict the response of the tumor from which they are derived. PDTO may thus be used as a tool to predict chemo-ICB efficacy in TNBC patients.

Method: The TRIPLEX study is a single-center observational study conducted to investigate the feasibility of generating PDTO from TNBC and to evaluate their ability to predict clinical response. PDTO will be obtained after the dissociation of biopsies and embedding into extra cellular matrix. PDTO will be cultured in a medium supplemented with growth factors and signal pathway inhibitors. Molecular and histological analyses will be performed on established PDTO lines to validate their phenotypic proximity with the original tumor. Response of PDTO to chemo-ICB will be assessed using co-cultures with autologous immune cells collected from patient blood samples. PDTO response will finally be compared with the response of the patient to evaluate the predictive potential of the model.

Discussion: This study will allow to assess the feasibility of using PDTO as predictive tools for the evaluation of the response of TNBC patients to treatments. In the event that PDTO could faithfully predict patient response in clinically relevant time frames, a prospective clinical trial could be designed to use PDTO to guide clinical decision. This study will also permit the establishment of a living biobank of TNBC PDTO usable for future innovative strategies evaluation.

Trial registration: The clinical trial (version 1.2) has been validated by local research ethic committee on December 30th 2021 and registered at ClinicalTrials.gov with the identifier NCT05404321 on June 3rd 2022, version 1.2.

Keywords: Chemo-immunotherapy; Patient-derived tumor organoids; Predictive functional assays; Triple negative breast cancer.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
TRIPLEX study design (created with Biorender.com)
Fig. 2
Fig. 2
PDTO generation and treatment (created with Biorender.com)
See this image and copyright information in PMC

References

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