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Highlights:

* Gastrin controls gastric acid secretion and mucosal cell growth via CCK2 receptors.

* CCK2RA can prevent/treat consequences of hypergastrinaemia or acid-related diseases.

* CCK2RA can eradicate type 1 NETs and reduce miR-222, which targets p27kip1.

* miR-222 is a potential biomarker for gastrin-induced gastric premalignant changes.

* There are many other potential clinical indications for a CCK2RA, and an unmet need.

: Gastrin controls gastric acid secretion and mucosal cell growth, especially of enterochromaffin-like cells, via gastrin/cholecystokinin-2 receptor (CCK2R) binding and downstream signalling. Studies in animal models, healthy subjects and patients with gastric neuroendocrine tumours provide compelling evidence to justify developing a CCK2R antagonist (CCK2RA) for preventing or treating the trophic effects of hypergastrinaemia or conditions expressing CCK2R, and with or without a proton pump inhibitor, for treating gastric acid-related conditions. Many compounds have been studied, but most have had problems with potency, selectivity for CCK2 versus CCK1 receptor, solubility or oral bioavailability. None has yet been marketed. Netazepide and Z-360 are currently undergoing clinical development, for treatment of gastric neuroendocrine tumours and pancreatic cancer, respectively. There are several other potential indications for a CCK2RA and an unmet need.

(C) 2016Elsevier, Inc.