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Review
. 2022 Jan;24(1):77-88.
doi: 10.1007/s11912-021-01175-y. Epub 2022 Jan 20.

New Developments in Gastric Neuroendocrine Neoplasms

Klaire Exarchou  1   2 , Nathan A Stephens  2 , Andrew R Moore  3 , Nathan R Howes  2 , D Mark Pritchard  4   5
Affiliations
Review

New Developments in Gastric Neuroendocrine Neoplasms

Klaire Exarchou et al. Curr Oncol Rep. 2022 Jan.

Abstract

Purpose of review: Gastric neuroendocrine neoplasms (g-NENs) are a rare type of stomach cancer. The three main subtypes have different pathogeneses, biological behaviours and clinical characteristics, so they require different management strategies. This article will provide an overview of g-NENs and highlight recent advances in the field.

Recent findings: Molecular profiling has revealed differences between indolent and aggressive g-NENs, as well as a new somatic mutation responsible for some familial type I g-NENs. Novel biomarkers have been developed which will hopefully improve diagnosis, treatment, risk stratification and follow-up. Patient treatment is also changing, as evidence supports the use of less aggressive options (e.g. endoscopic surveillance or resection) in some patients with more indolent tumours. g-NEN heterogeneity poses challenges in understanding and managing this rare disease. More basic science research is needed to investigate molecular pathogenesis, and future larger clinical studies will hopefully also further improve treatment and patient outcomes.

Keywords: Atrophic gastritis; Carcinoid; Enterochromaffin-like (ECL)-cell; Gastrin; Neuroendocrine tumour; stomach.

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Conflict of interest statement

Klaire Exarchou has received speaker’s honoraria from Ipsen. Nathan A. Stephens declares that he has no conflict of interest. Andrew R. Moore has received speaker’s honoraria from Dr. Falk Pharma GmbH, and has received reimbursement for travel accommodations/expenses from Ipsen. Nathan R. Howes is supported, in part, by a research grant from the UK and Ireland Neuroendocrine Tumour Society (UKINETS)/Neuroendocrine Cancer UK. D. Mark Pritchard is supported, in part, by a research grant from UKINETS/Neuroendocrine Cancer UK, and has received research funding to investigate the role of netazepide in gastric NETs from Trio Medicines Ltd.; has served as a consultant for Ipsen, Advanced Accelerator Applications, and Laboratoires Mayoly-Spindler, with all compensation going directly to his institution; has served as a guest lecturer/speaker/presenter for Ipsen, Advanced Accelerator Applications, and Laboratoires Mayoly-Spindler, with all compensation going directly to his institution; has received reimbursement for travel accommodations/expenses from Ipsen; has participated on a Data Safety Monitoring Board or Advisory Board for Ipsen and Advanced Accelerator Applications, with all compensation going directly to his institution; and was a member of the British Society of Gastroenterology Council from 2018 to 2020.

Figures

Fig. 1:
Fig. 1:
Pathophysiology of g-NENs. A Physiological gastric acid secretion: Antral G cells release gastrin after the ingestion of food. Gastrin binds to the CCK2 receptor on corpus-located enterochromaffin-like (ECL) cells, and this cell type then produces histamine. Histamine then binds to H2 receptors on gastric parietal cells resulting in stimulation of acid production and a reduction in the pH in the gastric lumen. This initiates an inhibitory feedback loop to downregulate gastrin release mediated by somatostatin-producing D cells which directly inhibits further release of gastrin from G cells. B Type I g-NENs: Loss of parietal cells disrupts the inhibitory loop leading to antral G cell hyperplasia and hypergastrinaemia. This leads to ECL-cell hyperplasia and eventually type I g-NEN formation. Potential treatment targets on the ECL cell are the CCK2 receptor and the somatostatin receptor (SSR). Netazepide irreversibly binds to the CCK2 receptor, and somatostatin analogues (SSAs) bind to the SSR with anti-proliferative effects. C Type II g-NENs: Ectopic G cell neoplasia leads to hypergastrinaemia and resultant excess gastric acid production that is independent of the normal inhibitory feedback loop. ECL cell and parietal cell hyperplasia are observed. D Type III g-NENs: Sporadic formation of g-NEN derived from ECL cells occurs with no evidence of hypergastrinaemia and no known disturbance of underlying gastric physiology. Created with BioRender.com
See this image and copyright information in PMC

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