title: Netazepide, a gastrin/cholecystokinin-2 receptor antagonist, can eradicate gastric neuroendocrine tumours in patients with autoimmune chronic atrophic gastritis.
abstract: Netazepide, a gastrin/cholecystokinin 2 receptor antagonist, once daily for 12 weeks reduced the number of tumours and size of the largest one in 16 patients with autoimmune chronic atrophic gastritis (CAG), achlorhydria, hypergastrinaemia and multiple gastric neuroendocrine tumours (type 1 gastric NETs), and normalized circulating chromogranin A (CgA) produced by enterochromaffin-like cells, the source of the tumours. The aim was to assess whether longer-term netazepide treatment can eradicate type 1 gastric NETs.
  
  
  
  After a mean 14 months off netazepide, 13 of the 16 patients took it for another 52 weeks. Assessments were: gastroscopy; gene-transcript expression in corpus biopsies using quantitative polymerase chain reaction; blood CgA and gastrin concentrations; and safety assessments.
  
  
  
  While off-treatment, the number of tumours, the size of the largest one, and CgA all increased again. Netazepide for 52 weeks: cleared all tumours in 5 patients; cleared all but one tumour in one patient; reduced the number of tumours and size of the largest one in the other patients; normalized CgA in all patients; and reduced mRNA abundances of CgA and histidine decarboxylase in biopsies. Gastrin did not increase further, confirming that the patients had achlorhydria. Netazepide was safe and well tolerated.
  
  
  
  A gastrin/cholecystokinin 2 receptor antagonist is a potential medical and targeted treatment for type 1 gastric NETs, and an alternative to regular gastroscopy or surgery. Treatment should be continuous because the tumours will regrow if it is stopped. Progress can be monitored by CgA in blood or biomarkers in mucosal biopsies.
authors.affiliation: Hammersmith Medicines Research, Cumberland Avenue, London, NW10 7EW, UK.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Boyce
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool, L69 3GE, UK.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Moore
authors.affiliation: Department of Gastroenterology and Hepatology, St. Olav's Hospital, and the Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Liv
authors.initials: L
authors.lastname: Sagatun
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool, L69 3GE, UK.
authors.forename: Bryony N
authors.initials: BN
authors.lastname: Parsons
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool, L69 3GE, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Varro
authors.affiliation: Department of Pathology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, L7 8XP, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Campbell
authors.affiliation: Department of Gastroenterology and Hepatology, St. Olav's Hospital, and the Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Reidar
authors.initials: R
authors.lastname: Fossmark
authors.affiliation: Department of Gastroenterology and Hepatology, St. Olav's Hospital, and the Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Helge L
authors.initials: HL
authors.lastname: Waldum
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool, L69 3GE, UK.
authors.forename: D Mark
authors.initials: DM
authors.lastname: Pritchard
mesh_terms: D000126:Achlorhydria / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D000368:Aged; D001327:Autoimmune Diseases / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D001570:Benzodiazepinones / Q000009:adverse effects / Q000627:therapeutic use*; D053379:Chromogranin A / Q000096:biosynthesis / Q000097:blood; D005755:Gastrins / Q000097:blood; D005757:Gastritis, Atrophic / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006640:Histidine Decarboxylase / Q000096:biosynthesis; D006801:Humans; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001570:Benzodiazepinones; D053379:Chromogranin A; D005755:Gastrins; D010671:Phenylurea Compounds; D006640:Histidine Decarboxylase; C104428:YF 476
keywords: chromogranin A; chronic atrophic gastritis; gastric neuroendocrine tumours; gastrin; gastrin/cholecystokinin-2 receptor antagonist; netazepide