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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00475

Pancreatic cancer organoids for determining sensitivity to Bromodomain and Extra-Terminal inhibitors (BETi)

 BENJAMIN BIAN1,  NATALIA A. JUIZ1, ODILE GAYET1,  MARTIN BIGONNET1, NICOLAS BRANDONE1, JULIE ROQUES1, JEROME CROS2, Nenghui Wang3,  Nelson J. Dusetti1 and  Juan Iovanna1*
  • 1INSERM U1068 Centre de recherche en cancérologie de Marseille, France
  • 2INSERM U1149 Centre de Recherche sur l'Inflammation, France
  • 3Ningbo Wenda Pharma Technology Ltd, China

Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous disease, therefore stratification of patients is essential to predict their responses to therapies and to choose the best treatment. PDAC-derived organoids were produced from PDTX and Endoscopic Ultrasound-Guided Fine-Needle Aspiration (EUS-FNA) biopsies. A signature based on 16 genes targets of the c-MYC oncogene were applied to classified samples into two sub-groups with distinctive phenotypes named MYC-high and MYC-low. The analysis of 9 PDTXs and the corresponding derived organoids reveled that this signature which was previously designed from PDTX is transferable to the organoid model. Primary organoids from 24 PDAC patients were treated with NHWD-870 or JQ1, two inhibitors of c-MYC transcription. Notably, the comparison of their effect between the two sub-groups showed that both compounds are more efficient in MYC-high than in MYC-low samples, being NHWD-870 the more potent treatment. In conclusion, this study shows that the molecular signatures could be applied to organoids obtained directly from PDAC patients to predict the treatment response and could help to take the more appropriate therapeutic decision for each patient in a clinical timeframe.

Keywords: Pancreatic Cancer, Organoids model, c-Myc, NHWD-870, JQ1

Received: 19 Mar 2019; Accepted: 17 May 2019.

Edited by:

John J. Tentler, School of Medicine, University of Colorado Denver, United States

Reviewed by:

Feng Wei, Tianjin Medical University Cancer Institute and Hospital, China
Toru Furukawa, School of Medicine, Tohoku University, Japan  

Copyright: © 2019 BIAN, JUIZ, GAYET, BIGONNET, BRANDONE, ROQUES, CROS, Wang, Dusetti and Iovanna. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Juan Iovanna, INSERM U1068 Centre de recherche en cancérologie de Marseille, Marseille, 13273, Provence-Alpes-Côte d'Azur, France, juan.iovanna@inserm.fr