The TRIPLEX study: use of patient-derived tumor organoids as an innovative tool for precision medicine in triple-negative breast 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...
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-023-11362-8 |
| _version_ | 1797452336151396352 |
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| author | Jordane Divoux Romane Florent Margaux Jacobs Justine Lequesne Jean-Michel Grellard Chankannira San Sara Grossi Katia Kerdja Bénédicte Clarisse Gwenaelle Boudier François Cherifi Mélanie Briand Enora Dolivet Alisson Johnson Brice Dubois Valentin Harter Joëlle Lacroix Charlotte Raboutet Brigitte Marie Nathalie Rousseau Cécile Blanc-Fournier Dominique Vaur Martin Figeac Laurent Poulain Louis-Bastien Weiswald George Emile |
| author_facet | Jordane Divoux Romane Florent Margaux Jacobs Justine Lequesne Jean-Michel Grellard Chankannira San Sara Grossi Katia Kerdja Bénédicte Clarisse Gwenaelle Boudier François Cherifi Mélanie Briand Enora Dolivet Alisson Johnson Brice Dubois Valentin Harter Joëlle Lacroix Charlotte Raboutet Brigitte Marie Nathalie Rousseau Cécile Blanc-Fournier Dominique Vaur Martin Figeac Laurent Poulain Louis-Bastien Weiswald George Emile |
| author_sort | Jordane Divoux |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T15:07:02Z |
| format | Article |
| id | doaj.art-ca31ade11a73463e975df48ff00e460c |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-09T15:07:02Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-ca31ade11a73463e975df48ff00e460c2023-11-26T13:35:53ZengBMCBMC Cancer1471-24072023-09-012311810.1186/s12885-023-11362-8The TRIPLEX study: use of patient-derived tumor organoids as an innovative tool for precision medicine in triple-negative breast cancerJordane Divoux0Romane Florent1Margaux Jacobs2Justine Lequesne3Jean-Michel Grellard4Chankannira San5Sara Grossi6Katia Kerdja7Bénédicte Clarisse8Gwenaelle Boudier9François Cherifi10Mélanie Briand11Enora Dolivet12Alisson Johnson13Brice Dubois14Valentin Harter15Joëlle Lacroix16Charlotte Raboutet17Brigitte Marie18Nathalie Rousseau19Cécile Blanc-Fournier20Dominique Vaur21Martin Figeac22Laurent Poulain23Louis-Bastien Weiswald24George Emile25INSERM U1086 ANTICIPE (Interdisciplinary Research Unit for Cancers Prevention and Treatment), BioTICLA Laboratory (Precision Medicine for Ovarian Cancers), Université de Caen NormandieINSERM U1086 ANTICIPE (Interdisciplinary Research Unit for Cancers Prevention and Treatment), BioTICLA Laboratory (Precision Medicine for Ovarian Cancers), Université de Caen NormandieComprehensive Cancer Center François Baclesse, Breast Cancer Unit, UNICANCER, Institut Normand du SeinComprehensive Cancer Center François Baclesse, Clinical Research Department, UNICANCERComprehensive Cancer Center François Baclesse, Clinical Research Department, UNICANCERComprehensive Cancer Center François Baclesse, Clinical Research Department, UNICANCERComprehensive Cancer Center François Baclesse, Clinical Research Department, UNICANCERComprehensive Cancer Center François Baclesse, Clinical Research Department, UNICANCERComprehensive Cancer Center François Baclesse, Clinical Research Department, UNICANCERComprehensive Cancer Center François Baclesse, Clinical Research Department, UNICANCERComprehensive Cancer Center François Baclesse, Breast Cancer Unit, UNICANCER, Institut Normand du SeinINSERM U1086 ANTICIPE (Interdisciplinary Research Unit for Cancers Prevention and Treatment), BioTICLA Laboratory (Precision Medicine for Ovarian Cancers), Université de Caen NormandieINSERM U1086 ANTICIPE (Interdisciplinary Research Unit for Cancers Prevention and Treatment), BioTICLA Laboratory (Precision Medicine for Ovarian Cancers), Université de Caen NormandieComprehensive Cancer Center François Baclesse, Breast Cancer Unit, UNICANCER, Institut Normand du SeinComprehensive Cancer Center François Baclesse, North-West Canceropole Data Center, UNICANCERComprehensive Cancer Center François Baclesse, North-West Canceropole Data Center, UNICANCERComprehensive Cancer Center François Baclesse, Department of Radiology, UNICANCERComprehensive Cancer Center François Baclesse, Department of Radiology, UNICANCERComprehensive Cancer Center François Baclesse, Department of Radiology, UNICANCERComprehensive Cancer Center François Baclesse, UNICANCERINSERM U1086 ANTICIPE (Interdisciplinary Research Unit for Cancers Prevention and Treatment), BioTICLA Laboratory (Precision Medicine for Ovarian Cancers), Université de Caen NormandieComprehensive Cancer Center François Baclesse, Department of Cancer Biology and Genetics, UNICANCERCNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41 - UAR 2014 - PLBS, University of LilleINSERM U1086 ANTICIPE (Interdisciplinary Research Unit for Cancers Prevention and Treatment), BioTICLA Laboratory (Precision Medicine for Ovarian Cancers), Université de Caen NormandieINSERM U1086 ANTICIPE (Interdisciplinary Research Unit for Cancers Prevention and Treatment), BioTICLA Laboratory (Precision Medicine for Ovarian Cancers), Université de Caen NormandieComprehensive Cancer Center François Baclesse, Breast Cancer Unit, UNICANCER, Institut Normand du SeinAbstract 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.https://doi.org/10.1186/s12885-023-11362-8Triple negative breast cancerPatient-derived tumor organoidsPredictive functional assaysChemo-immunotherapy |
| spellingShingle | Jordane Divoux Romane Florent Margaux Jacobs Justine Lequesne Jean-Michel Grellard Chankannira San Sara Grossi Katia Kerdja Bénédicte Clarisse Gwenaelle Boudier François Cherifi Mélanie Briand Enora Dolivet Alisson Johnson Brice Dubois Valentin Harter Joëlle Lacroix Charlotte Raboutet Brigitte Marie Nathalie Rousseau Cécile Blanc-Fournier Dominique Vaur Martin Figeac Laurent Poulain Louis-Bastien Weiswald George Emile The TRIPLEX study: use of patient-derived tumor organoids as an innovative tool for precision medicine in triple-negative breast cancer BMC Cancer Triple negative breast cancer Patient-derived tumor organoids Predictive functional assays Chemo-immunotherapy |
| title | The TRIPLEX study: use of patient-derived tumor organoids as an innovative tool for precision medicine in triple-negative breast cancer |
| title_full | The TRIPLEX study: use of patient-derived tumor organoids as an innovative tool for precision medicine in triple-negative breast cancer |
| title_fullStr | The TRIPLEX study: use of patient-derived tumor organoids as an innovative tool for precision medicine in triple-negative breast cancer |
| title_full_unstemmed | The TRIPLEX study: use of patient-derived tumor organoids as an innovative tool for precision medicine in triple-negative breast cancer |
| title_short | The TRIPLEX study: use of patient-derived tumor organoids as an innovative tool for precision medicine in triple-negative breast cancer |
| title_sort | triplex study use of patient derived tumor organoids as an innovative tool for precision medicine in triple negative breast cancer |
| topic | Triple negative breast cancer Patient-derived tumor organoids Predictive functional assays Chemo-immunotherapy |
| url | https://doi.org/10.1186/s12885-023-11362-8 |
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