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Updated: Aug 26, 2026
Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor
Published on: May 2, 2022
High expression of peptide receptors as a novel target in gastrointestinal stromal tumours
Jean Claude Reubi1, Meike Körner, Beatrice Waser
1Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Murtenstrasse 31, PO Box 62, 3010 Bern, Switzerland. reubi@pathology.unibe.ch
Abstract:
Recent significant advances in understanding the biology of gastrointestinal stromal tumours (GIST) have led to the introduction of a new targeted therapy (imatinib mesylate, Glivec). Hopes of a new era of a specific cancer therapy, however, have been tempered by the recognition that a significant proportion of patients who initially respond to the drug eventually become resistant to it. Given the successful development of peptide receptor scintigraphy and radiotherapy for neuroendocrine tumours, we postulated that a similar approach could offer a valid alternative in the diagnosis and therapy of GIST. Using in vitro receptor autoradiography to measure peptide receptors, we found that 16/19 GIST expressed bombesin subtype 2 receptors, 16/19 expressed vasoactive intestinal peptide subtype 2 receptors (VPAC(2)) and 12/19 expressed cholecystokinin subtype 2 receptors, in most cases in extremely high densities. All GIST metastases were shown to express two or more of these peptide receptors in very high density. Receptors were also expressed in non-responders to Glivec or after chemo-embolisation. Conversely, somatostatin subtype 2, cholecystokinin subtype 1, bombesin subtype 1 and 3, and neuropeptide Y subtype Y(1) and Y(2) receptors were not or only rarely expressed. These data represent a strong molecular basis for the use of radiolabelled bombesin, vasoactive intestinal peptide and/or cholecystokinin analogues as targeting agents to localise GIST tumours in patients by in vivo scintigraphy and/or to perform targeted radiotherapy to destroy GIST primaries, metastases and recurrences, including those resistant to Glivec.
Insights
Gastrointestinal stromal tumours (GIST) express high levels of specific peptide receptors. These receptors offer new diagnostic and therapeutic strategies for GIST, including drug-resistant cases.
Area of Science:
- Oncology
- Molecular Biology
- Radiology
Background:
- Gastrointestinal stromal tumours (GIST) are increasingly understood, leading to targeted therapies like imatinib mesylate.
- Therapy resistance develops in a significant proportion of GIST patients, necessitating alternative treatment strategies.
- Peptide receptor-targeted therapies have shown success in neuroendocrine tumours, suggesting potential for GIST.
Purpose of the Study:
- To investigate the expression of peptide receptors on GIST.
- To evaluate the potential of peptide receptor-targeted agents for GIST diagnosis and therapy.
- To identify molecular targets for GIST treatment beyond imatinib resistance.
Main Methods:
- In vitro receptor autoradiography was used to quantify peptide receptor expression on GIST samples.
- Analysis included GIST primaries, metastases, and samples from patients with varying treatment responses.
- Receptor expression levels were compared across different GIST subtypes and treatment statuses.
Main Results:
- A high prevalence of bombesin subtype 2, vasoactive intestinal peptide subtype 2 (VPAC(2)), and cholecystokinin subtype 2 receptors was observed in GIST.
- These receptors were often expressed at extremely high densities, particularly on GIST metastases.
- Receptor expression persisted in GIST resistant to imatinib mesylate or after chemoembolization.
Conclusions:
- GIST exhibits significant expression of specific peptide receptors, forming a strong molecular basis for targeted therapies.
- Radiolabeled bombesin, vasoactive intestinal peptide, and cholecystokinin analogues can be utilized for GIST localization via scintigraphy.
- These agents hold promise for targeted radiotherapy of GIST, including primary tumors, metastases, and imatinib-resistant or recurrent disease.
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