Research Papers:

A subgroup of pancreatic adenocarcinoma is sensitive to the 5-aza-dC DNA methyltransferase inhibitor

Odile Gayet _, Celine Loncle, Pauline Duconseil, Marine Gilabert, Maria Belen Lopez, Vincent Moutardier, Olivier Turrini, Ezequiel Calvo, Jacques Ewald, Marc Giovannini, Mohamed Gasmi, Erwan Bories, Marc Barthet, Mehdi Ouaissi, Anthony Goncalves, Flora Poizat, Jean Luc Raoul, Veronique Secq, Stephane Garcia, Patrice Viens, Nelson Dusetti and Juan Iovanna

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Oncotarget. 2015; 6:746-754. https://doi.org/10.18632/oncotarget.2685

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Odile Gayet1, Celine Loncle1, Pauline Duconseil1, Marine Gilabert1, Maria Belen Lopez1, Vincent Moutardier1,2, Olivier Turrini1,3, Ezequiel Calvo4, Jacques Ewald3, Marc Giovannini3, Mohamed Gasmi5, Erwan Bories3, Marc Barthet5, Mehdi Ouaissi6, Anthony Goncalves3, Flora Poizat3, Jean Luc Raoul3, Veronique Secq1,2, Stephane Garcia1,2, Patrice Viens3, Nelson Dusetti1, Juan Iovanna1

1Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France

2Hôpital Nord, Marseille, France

3Institut Paoli-Calmettes, Marseille, France

4Centre Génomique du Centre de recherche du CHUL Research Center, Quebec, Canada

5Hôpital Nord, Département de Gastroentérologie, Marseille, France

6Hôpital de la Timone, Marseille, France

Correspondence to:

Nelson Dusetti, e-mail: nelson.dusetti@inserm.fr

Juan Iovanna, e-mail: juan.iovanna@inserm.fr

Received: August 05, 2014     Accepted: November 02, 2014     Published: December 03, 2014


Pancreatic Ductal Adenocarcinoma (PDAC) is a disease with a great heterogeneity in the response to treatments. To improve the responsiveness to treatments there are two different approaches, the first one consist to develop new and more efficient drugs that intent to cure all patients and the second one is to use already-approved drugs, alone or in combination, but selecting beforehand the most sensitive patients. In this work we explored the efficiency of the second possibility. We developed a collection of 17 PDAC samples collected by Endoscopic Ultrasound-Guided Fine-Needle Aspiration (EUS-FNA) or surgery and preserved as xenografts and as primary cultures. This collection was characterized at molecular level by a transcriptomic analysis using an Affymetrix approach. In this paper we present data demonstrating that a subgroup of PDAC responds to low doses of 5-aza-dC. These tumors show a specific RNA expression profile that could serve as a marker, but there is no correlation with Dnmt1, Dnmt3A or Dnmt3B expression. Responder tumors corresponded to well-differentiated samples and longer survival patients. In conclusion, we present data obtained with the well-known drug 5-aza-dC as a proof of concept that a drug that seems to be inefficient in solid tumors in general could be applicable to a particular subgroup of patients with PDAC.

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