Role of progastrins and gastrins and their receptors in GI and pancreatic cancers: Targets for treatment

William Rengifo-Cam, Pomila Singh

Research output: Contribution to journalReview article

41 Scopus citations

Abstract

Accumulating evidence in literature suggests that amidated and non-amidated gastrins (gastrin precursors) may play an important role in the proliferation and carcinogenesis of gastrointestinal and pancreatic cancers, especially in the presence of DNA damaging agents and/or infectious agents. Amidated gastrins appear to have a protective role, while progastrins exert growth promoting effects in cancers. Several receptor subtypes and signal transduction pathways mediate the biological effects of the gastrin peptides. Progastrin and gastrins also exert anti-apoptotic effects, which may additionally contribute to the growth and co-carcinogenic effects of these peptides on GI mucosal cells in vivo. Amidated gastrins additionally play an important role in the migration of GI epithelial cells, and in glandular morphogenesis, while progastrins may play an important role in invasion and metastasis. Therefore, targeting progastrins, gastrins, and their cognate receptors may provide a therapeutic tool for treating GI and pancreatic cancers. Targeting CCK2-receptors has, so far, not provided optimal beneficial effects. However, targeting gastrins via a vaccine approach has provided some encouraging results for treating GI and pancreatic cancers. It is expected that targeting precursor gastrins (progastrins and gly-gastrins), exclusively rather than amidated gastrins, may be more effective for treating GI cancers. Since GI cancers at advanced stages are largely responsive to autocrine and intracrine progastrins, down-regulation of intracellular progastrins will likely be more effective at this stage.

Original languageEnglish (US)
Pages (from-to)2345-2358
Number of pages14
JournalCurrent Pharmaceutical Design
Volume10
Issue number19
DOIs
StatePublished - Jul 14 2004

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Keywords

  • CCK-2 receptor
  • Colon carcinogenesis
  • Gastric cancers
  • Gastrin gene expression
  • Progastrin receptor
  • Signaling
  • Vaccines

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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