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Review article: gastrin and colorectal cancer
1The Academic Unit of Cancer Studies, Department of Surgery, University Hospital, Nottingham, UK. ANDREW.SMITH@NOTTINGHAM.AC.UK
Alimentary Pharmacology & Therapeutics
|September 30, 2000
Summary
Gastrin, a hormone regulating acid secretion, also promotes growth and is implicated in colorectal cancer. Research clarifies its autocrine role in tumor development and potential as a therapeutic target.
Area of Science:
- Gastroenterology
- Oncology
- Endocrinology
Background:
- Gastrin, a polypeptide hormone, is known for regulating gastric acid secretion and acting as a growth factor for gastric mucosa.
- Its growth-promoting action has prompted investigation into its role in carcinogenesis, particularly colorectal neoplasia.
- The precise relationship between gastrin and colorectal adenocarcinoma has been a subject of debate, but recent studies offer clearer insights.
Purpose of the Study:
- To elucidate the mechanism of gastrin's action in colorectal cancer.
- To explore the role of autocrine gastrin production and gastrin/CCKB receptors in tumor proliferation.
- To evaluate gastrin as a therapeutic target for colorectal cancer treatment.
Main Methods:
- Review of recent studies investigating gastrin's role in colorectal neoplasia.
- Analysis of findings from animal models and human epidemiological studies on hypergastrinaemia and colorectal cancer.
- Assessment of various therapeutic approaches targeting gastrin, including receptor antagonists, antisecretory agents, and anti-gastrin antibodies.
Main Results:
- The majority of colorectal cancers produce gastrin, potentially acting in an autocrine manner via gastrin/CCKB receptors to mediate proliferation.
- Autocrine gastrin expression is observed early in the adenoma-carcinoma sequence, suggesting a role in tumor development.
- Systemic hypergastrinaemia, observed in humans and demonstrated in animal models, promotes colonic epithelial proliferation and is linked to increased colorectal cancer incidence.
Conclusions:
- Gastrin plays a significant role in colorectal cancer development and progression through autocrine signaling and by promoting epithelial proliferation.
- While receptor antagonists and antisecretory agents have proven ineffectual, novel therapeutic strategies like anti-gastrin antibodies are under evaluation.
- Gastrin represents a promising therapeutic target for colorectal cancer, with ongoing research focused on effective inhibition methods.