Section Review: Oncologic, Endocrine & Metabolic: Gastrin antagonists and gastrointestinal tumours

Abstract

The role of gastrin in the growth of gastrointestinal tumours is complex, involving both endocrine and autocrine/paracrine pathways. Receptor subtypes, distinct from the classical gastrin/CCK-B receptors which mediate the normal physiological functions of gastrin, are now being identified. These appear to have potential roles in gastrin-associated proliferative pathways in malignant cells. Due to the recent expansion of knowledge in this area, the role of the classical anti-gastrin agents remains unclear. This is especially so for the gastrin/CCK-B receptor antagonists, due to the multiple receptor types now in evidence. However, certain agents may potentially overcome the problem of the different gastrin-mediated mitogenic pathways and the receptor isoforms involved. Although agents which block gastrin secretion, such as somatostatin analogues, might have been expected to be successful at targeting the autocrine/paracrine pathway, clinically, in gastrointestinal adenocarcinomas, they have proven disappointing. This may possibly be due to low tumour expression of the relevant somatostatin receptor subtypes. Antibody neutralisation of mitogenic forms of gastrin by use of gastrin immunogens may have therapeutic potential in the clinic but has so far only been evaluated in a pre-clinical setting.

CCK-A receptor antagonists have low affinity for gastrin receptors and information on CCK-A receptor antagonists and Gl cancers is scarce. Consequently, this review concentrates on the effects of gastrin/CCK-B receptor antagonists in Gl cancers.