title: A subgroup of pancreatic adenocarcinoma is sensitive to the 5-aza-dC DNA methyltransferase inhibitor.
abstract: 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.
authors.affiliation: Centre 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.
authors.forename: Odile
authors.initials: O
authors.lastname: Gayet
authors.affiliation: Centre 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.
authors.forename: Celine
authors.initials: C
authors.lastname: Loncle
authors.affiliation: Centre 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.
authors.forename: Pauline
authors.initials: P
authors.lastname: Duconseil
authors.affiliation: Centre 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.
authors.forename: Marine
authors.initials: M
authors.lastname: Gilabert
authors.affiliation: Centre 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.
authors.forename: Maria Belen
authors.initials: MB
authors.lastname: Lopez
authors.affiliation: Centre 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.|Hôpital Nord, Marseille, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Moutardier
authors.affiliation: Centre 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.|Institut Paoli-Calmettes, Marseille, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Turrini
authors.affiliation: Centre Génomique du Centre de recherche du CHUL Research Center, Quebec, Canada.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Calvo
authors.affiliation: Institut Paoli-Calmettes, Marseille, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Ewald
authors.affiliation: Institut Paoli-Calmettes, Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Giovannini
authors.affiliation: Hôpital Nord, Département de Gastroentérologie, Marseille, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Gasmi
authors.affiliation: Institut Paoli-Calmettes, Marseille, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Bories
authors.affiliation: Hôpital Nord, Département de Gastroentérologie, Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Barthet
authors.affiliation: Hôpital de la Timone, Marseille, France.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ouaissi
authors.affiliation: Institut Paoli-Calmettes, Marseille, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Goncalves
authors.affiliation: Institut Paoli-Calmettes, Marseille, France.
authors.forename: Flora
authors.initials: F
authors.lastname: Poizat
authors.affiliation: Institut Paoli-Calmettes, Marseille, France.
authors.forename: Jean Luc
authors.initials: JL
authors.lastname: Raoul
authors.affiliation: Centre 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.|Hôpital Nord, Marseille, France.
authors.forename: Veronique
authors.initials: V
authors.lastname: Secq
authors.affiliation: Centre 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.|Hôpital Nord, Marseille, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Garcia
authors.affiliation: Institut Paoli-Calmettes, Marseille, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
authors.affiliation: Centre 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.
authors.forename: Nelson
authors.initials: N
authors.lastname: Dusetti
authors.affiliation: Centre 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.
authors.forename: Juan
authors.initials: J
authors.lastname: Iovanna
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000494:pharmacology*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors*; D000090205:DNA Methyltransferase 3A; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D059467:Transcriptome; D023041:Xenograft Model Antitumor Assays; D000097584:DNA Methyltransferase 3B
chemical_list: D001374:Azacitidine; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D004791:Enzyme Inhibitors; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C000715535:Dnmt3a protein, mouse; C000619380:DNMT1 protein, human; C000619381:Dnmt1 protein, mouse