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

胰腺腺癌的一个亚组对 5-aza-dC DNA 甲基转移酶抑制剂敏感

阅读:15
作者: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

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.

特别声明

1、本页面内容包含部分的内容是基于公开信息的合理引用;引用内容仅为补充信息,不代表本站立场。

2、若认为本页面引用内容涉及侵权,请及时与本站联系,我们将第一时间处理。

3、其他媒体/个人如需使用本页面原创内容,需注明“来源:[生知库]”并获得授权;使用引用内容的,需自行联系原作者获得许可。

4、投稿及合作请联系:info@biocloudy.com。