Inhibition of the BMP pathway prevents development of Barrett’s-associated adenocarcinoma in a surgical rat model

• Published in: Diseases of the esophagus 2022-05, Vol.35 (5)
• Main Authors: Westra, Wytske M, Straub, Danielle, Milano, Francesca, Buttar, Navtej S, Wang, Kenneth K, Krishnadath, Kausilia K
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 1120-8694; 1442-2050
• DOI: 10.1093/dote/doab072

Summary Introduction Esophageal adenocarcinoma (EAC) is an aggressive cancer, associated with reflux esophagitis and intestinal metaplasia (IM). One underlying biological mechanism, which possibly drives the development of EAC, is the dysregulated expression of Bone Morphogenetic Proteins (BMPs). Aim To investigate if local delivery of Noggin, a BMP antagonist, reduced EAC. Methods After obtaining proof of principal on local delivery of a Noggin/Sucralfate substance, a randomized controlled trial to test the effects of Noggin on EAC development was performed in a surgical rat model. In the model, an esophago-jejunostomy leads to development of reflux-esophagitis, IM and eventually EAC. Rats were treated by Noggin/Sucralfate or Sucralfate alone. Treatment was administered from 26 to 29 weeks after the operation. Results Of the 112 operated rats, 52 survived beyond 26 weeks. Finally, 25 rats treated with Noggin/Sucralfate and 21 with Sucralfate, were evaluated. At the end, 39 (85%) of the animals had IM while 28 (61%) developed cancer. There were significantly more cancers in the Noggin/Sucralfate arm (50%) versus the Sucralfate group (73%) (Chi square, P