The Role of PGE2 and its Corresponding Receptors (Ep1-4) in Oesophageal Carcinogenesis: Novel Therapeutics for Chemoprevention and/or Intervention
Michelle C. Lowry*, John V. Reynolds and Mary-Clare Cathcart
Department of Surgery, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St. James’s Hospital, Dublin, Ireland
- *Corresponding Author:
- Mary-Clare Cathcart
Department of Surgery, Institute of Molecular Medicine
Trinity Centre for Health Sciences
St. James’s Hospital, Dublin 8, Ireland
Tel: +353 1896 3620
E-mail: [email protected]
Received date: July 05, 2014; Accepted date: July 20, 2014; Published date: July 30, 2014
Citation: Lowry MC, Reynolds JV, Cathcart MC (2014) The Role of PGE2 and its Corresponding Receptors (Ep1-4) in Oesophageal Carcinogenesis: Novel Therapeutics for Chemoprevention and/or Intervention. J Carcinog Mutagen 5:181. doi: 10.4172/2157-2518.1000181
Copyright: © 2014 Lowry MC, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The incidence of oesophageal adenocarcinoma (OAC) is increasing. At present, OAC is the 7th leading cause of cancer deaths worldwide. The use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) reduce the progression from Barrett’s oesophagus (BO) to OAC. These cyclooxygenase (COX) targeted agents have demonstrated considerable promise, although long-term use has been associated with both gastrointestinal (GI) damage and increased cardiovascular risk. COX-2 overexpression is seen in BO and OAC patients and is a promising target for chemopreventive and/or therapeutic approaches. However, the unfavourable safety profile associated with long-term COX-2 targeting emphasizes the need to both understand and target specific downstream effector mechanisms. The role of pro-inflammatory prostaglandin E2 (PGE2) and its corresponding EP receptors have gained considerable attention in recent years, where they have been associated with tumourogenesis in a number of inflammatory-driven cancers, including OAC. This review will discuss the role of COX-derived PGE2 signalling in OAC development and progression, with specific emphasis on EP receptor expression and function. We will compare and contrast the potential of traditional NSAIDs, selective COX-2 inhibitors and EP antagonists as chemopreventive and/or therapeutic agents. Finally, we will discuss the promise of novel small molecule selective EP antagonists, which have recently been developed and are currently under clinical investigation.