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An Orthotopic Resectional Mouse Model of Pancreatic Cancer
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Reflections on some pilot trials of gastrin receptor blockade in pancreatic cancer
1King's College London, School of Medicine, 125 Coldharbour Lane, London SE5 9NU, United Kingdom. James.black@kcl.ac.uk
Abstract:
The experience of synthesising a novel gastrin receptor antagonist gastrazole and taking it into 3 small clinical studies in pancreatic cancer in man is described. The need for such a compound is illustrated by the observation that inhibition of gastric acid secretion by H2 receptor antagonists results in hypergastrinaemia. A large number of cell types have gastrin receptors including pancreatic cancer cells which have been shown to be stimulated by gastrin. Small numbers of pancreatic cancer patients given gastrazole by continuous intravenous infusion showed prolonged survival compared with best supportive care or placebo, and equivalent survival to those given 5 fluouracil. The results suggest a greater benefit for patients with early stage disease. An alternative gastrin receptor antagonist YF 476 is also described which has the advantage of efficacy given by the oral route. This new compound requires to be studied in pancreatic cancer and other diseases associated with hypergastrinaemia.
Insights
Gastrazole, a novel gastrin receptor antagonist, demonstrated prolonged survival in pancreatic cancer patients. This finding highlights its potential, especially in early-stage disease, offering a new avenue for cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Gastroenterology
Background:
- Hypergastrinaemia, resulting from H2 receptor antagonist use, indicates a need for gastrin receptor antagonists.
- Gastrin receptors are present on various cell types, including pancreatic cancer cells, which are stimulated by gastrin.
Purpose of the Study:
- To describe the synthesis and clinical evaluation of gastrazole, a novel gastrin receptor antagonist.
- To assess the efficacy of gastrazole in patients with pancreatic cancer.
Main Methods:
- Synthesis of the novel gastrin receptor antagonist, gastrazole.
- Conducting 3 small clinical studies in human pancreatic cancer patients.
- Administering gastrazole via continuous intravenous infusion.
Main Results:
- Prolonged survival observed in pancreatic cancer patients treated with gastrazole compared to placebo or best supportive care.
- Gastrazole showed equivalent survival rates to 5-fluorouracil in treated patients.
- Results suggest a more significant benefit for patients with early-stage pancreatic cancer.
Conclusions:
- Gastrazole demonstrates potential as a therapeutic agent for pancreatic cancer.
- The findings support further investigation of gastrazole and similar compounds in pancreatic cancer and hypergastrinaemia-associated diseases.
- An alternative oral gastrin receptor antagonist, YF 476, warrants study in pancreatic cancer.
