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Understanding How Type 1 Gastric Neuroendocrine Tumours Develop

May 24, 2021

Each year, Neuroendocrine Cancer UK offer a research grant to the UK’s medical research community, and we publish an update on the work undertaken and projects achieved by our Grant Awardees. This month, we’re featuring an update by Mark PritchardProfessor of Gastroenterology at the University of Liverpool and Head of the Department of Cellular and Molecular Physiology. Prof Pritchard is also a great supporter of NCUK and you will often see him taking part in our Educational Events for patients.

Understanding How Type I Gastric Neuroendocrine Tumours Develop

Prof Mark Pritchard, University of Liverpool. Research Grant 2014 & 2019 Awardee Project Update.

There are three main types of neuroendocrine tumour (NET) that develop in the stomach. The commonest type (type 1) develops in patients who have an autoimmune condition that results in destruction of the acid producing (parietal) cells in the stomach. Many type 1 gastric NET patients also have pernicious anaemia and require regular vitamin B12 injections. As a result of their stomachs producing little or no acid, these patients have very high levels of a hormone called gastrin in their bloodstream and it is this hormone that is believed to be responsible for the development of type 1 gastric NETs.

The long term outlook for most patients who have type 1 gastric NETs is very good. The majority of patients have small tumours and don’t actually need any type of active treatment. However a minority of patients have larger tumours and these may need to be removed either via an endoscope or by surgery. In 2010-4 we conducted a clinical trial involving eight patients in Liverpool and eight in Norway to test a potential new tablet treatment for type I gastric NETs (funded by Trio Medicines Ltd). If successful, this might mean that in future some type I gastric NET patients might be able to avoid surgery. The new drug (Netazepide) blocks the effects of gastrin. The trial showed promising results with a shrinkage in the size and number of the tumours in many patients and the treatment also resulted in no serious side effects 1,2. Trio medicines Ltd are still working on the development of this drug, so at the moment it is not available for general prescription.

In 2014, we were awarded a research grant by Neuroendocrine Cancer UK to investigate how Netazepide was exerting its effects in these patients. We used stomach biopsy samples that had been taken before, during and after the patients on this trial were being treated with Netazepide. We found that only 12 genes showed significantly decreased expression when the patients were taking Netazepide. One of these genes called pappalysin or PAPP-A2 was particularly interesting. This gene encodes a protein which is an enzyme that regulates how much of a growth factor called insulin-like growth factor is present in the stomach. We performed several additional experiments which demonstrated that this signalling pathway appears to both be important during gastric NET development and in determining how these tumours respond to Netazepide treatment. As well as increasing our scientific understanding about type I gastric NETs, our research has at least partially explained how Netazepide works and it also provides opportunities to design other potential new drug treatments for type I gastric NETs in the future.

The results of our study were published in the scientific journal ‘Cellular and Molecular Gastroenterology and Hepatology’ in 2020 and are available online to read by anyone who is interested 3.

In 2019 we were awarded another grant by Neuroendocrine Cancer UK to try to grow gastric NET cells in the laboratory in order to be able to test the effects of potential new treatments before actually giving these drugs to patients within a clinical trial. This research is still ongoing and we hope to provide an update about our findings in due course.


1. Moore AR, Boyce M, Steele IA, Campbell F, Varro A, Pritchard DM. Netazepide, a gastrin receptor antagonist, normalises tumour biomarkers and causes regression of type 1 gastric neuroendocrine tumours in a nonrandomised trial of patients with chronic atrophic gastritis. PLoS One. 2013;8(10):e76462.

2. Boyce M, Moore AR, Sagatun L, et al. Netazepide, a gastrin/cholecystokinin-2 receptor antagonist, can eradicate gastric neuroendocrine tumours in patients with autoimmune chronic atrophic gastritis. Br J Clin Pharmacol. 2017;83(3):466-475.

3. Lloyd KA, Parsons BN, Burkitt MD, et al. Netazepide Inhibits Expression of Pappalysin 2 in Type 1 Gastric Neuroendocrine Tumors. Cell Mol Gastroenterol Hepatol. 2020;10(1):113-132.