Gastric Cancer Pathophysiology and Hormonal Regulation

Gastric cancer arises through a multistep process that links chronic mucosal injury to altered hormonal signalling and cellular proliferation. Initial insults, most notably infection with Helicobacter pylori or autoimmune gastritis, provoke chronic inflammation and progressive loss of acid-secreting oxyntic glands. Resultant hypoacidity drives sustained hypergastrinemia, which in turn stimulates proliferation of enterochromaffin-like (ECL) cells via the gastrin (cholecystokinin-B) receptor. Over time, ECL cell hyperplasia may evolve through dysplasia into neuroendocrine tumours or adenocarcinoma. Parallel changes in stem-cell compartments and mucosal architecture give rise to intestinal- and diffuse-type carcinomas, each displaying distinct growth patterns and molecular profiles. Hormonal regulation is therefore central to gastric carcinogenesis: gastrin acts both as a mitogen and trophic factor, while somatostatin and other paracrine mediators serve inhibitory roles. External modifiers—proton pump inhibitors, dietary factors and eradication of H. pylori—modulate gastrin release and mucosal repair, presenting opportunities for prevention and early intervention. Emerging understanding of gastrin’s receptor signalling and ECL cell lineage offers new avenues for targeted therapies, including gastrin antagonists and immunomodulatory approaches.

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Gastric Cancer Pathophysiology and Hormonal Regulation publication trend

The graph below shows the total number of articles in gastric cancer pathophysiology and hormonal regulation across all publications each year (not limited to Nature Index journals).

Technical terms

Atrophic gastritis: Chronic inflammation leading to loss of acid-secreting oxyntic glands.

Gastrin: A peptide hormone produced by antral G cells that stimulates acid secretion and mucosal growth.

Hypergastrinemia: Elevated circulating gastrin levels resulting from hypoacidity or glandular atrophy.

Enterochromaffin-like (ECL) cell: A gastric neuroendocrine cell that releases histamine in response to gastrin and proliferates under trophic stimuli.

Cholecystokinin-B (CCK-B) receptor: The G-protein-coupled receptor on ECL cells that mediates gastrin’s mitogenic effects.

Neuroendocrine tumour (NET): A neoplasm arising from hormone-secreting cells, in this context often evolving from ECL cell hyperplasia.

References

1. Types of Gastric Carcinomas. International Journal of Molecular Sciences (2018).
2. Expression of the Cholecystokinin-B Receptor in Neoplastic Gastric Cells. Discover Oncology (2017).
3. The Enterochromaffin-like [ECL] Cell—Central in Gastric Physiology and Pathology. International Journal of Molecular Sciences (2019).
4. Hypergastrinemia is associated with an increased risk of gastric adenocarcinoma with proximal location: A prospective population‐based nested case‐control study. International Journal of Cancer (2020).
5. Towards Understanding of Gastric Cancer Based upon Physiological Role of Gastrin and ECL Cells. Cancers (2020).
6. The central role of gastrin in gastric cancer. Frontiers in Oncology (2023).
7. Gastrin Vaccine Alone and in Combination With an Immune Checkpoint Antibody Inhibits Growth and Metastases of Gastric Cancer. Frontiers in Oncology (2021).
8. CHRONIC USE OF PROTON PUMP INHIBITORS AND THE QUANTITY OF G, D, AND ECL CELLS IN THE STOMACH. ABCD Arquivos Brasileiros de Cirurgia Digestiva (São Paulo) (2020).
9. Correct Identification of Cell of Origin May Explain Many Aspects of Cancer: The Role of Neuroendocrine Cells as Exemplified from the Stomach. International Journal of Molecular Sciences (2020).