CCK2 receptor (gastrin receptor)
A docking site for the hormone gastrin, found at very high numbers on medullary thyroid cancer cells. Minigastrin-like radioactive drugs can bind it to find or treat that cancer, though they also light up the stomach because the same receptor lines it normally.
Overview
CCK2R is a G-protein-coupled receptor for the hormones gastrin and cholecystokinin, expressed physiologically in the gastric mucosa where it regulates acid secretion, and in parts of the central nervous system. It is overexpressed at very high incidence and density in medullary thyroid carcinoma (MTC) - historically detected indirectly through the pentagastrin stimulation test - and also occurs in a substantial minority of small-cell lung cancers, astrocytomas, stromal ovarian cancers, gastrointestinal stromal tumours and some gastroenteropancreatic neuroendocrine tumours.
Radiolabelled analogues of minigastrin, which retains the C-terminal receptor-binding tetrapeptide sequence (Trp-Met-Asp-Phe-NH2) common to gastrin and CCK, have been developed for both imaging (111In-, 99mTc-, or 68Ga-labelled minigastrin analogues, including Demogastrin 2 and MGS5) and therapy (90Y- or 177Lu-labelled minigastrin, such as 177Lu-PP-F11N). In patients with metastatic MTC, CCK2R-targeted imaging has detected more lesions than somatostatin receptor imaging, reflecting the low SSTR expression typical of MTC.
As a target, CCK2R's strength is very high density (over 90% of MTCs) and no competing standard-of-care radiotracer. Its central weakness, which has so far limited therapeutic use, is that the stomach expresses CCK2R physiologically and receives a comparable or higher radiation dose than the tumour with agonist-based minigastrin analogues, making the stomach dose-limiting; kidney and bone-marrow toxicity have also constrained early therapy trials, and receptor antagonist-based ligands (for example those built on nastorazepide) are being explored as an alternative with potentially better tumour-to-stomach ratios.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · A docking site for the hormone gastrin, found at very high numbers on medullary thyroid cancer cells. Minigastrin-like radioactive drugs can bind it to find or treat that cancer, though they also light up the stomach because the same receptor lines it normally.
- 1 · What it is
A docking site for the hormone gastrin, found at very high numbers on medullary thyroid cancer cells. Minigastrin-like radioactive drugs can bind it to find or treat that cancer, though they also light up the stomach because the same receptor lines it normally.
- 2 · What goes wrong in cancer
A G-protein-coupled receptor for gastrin and cholecystokinin that physiologically regulates gastric acid secretion.
- 3 · How drugs use it
No product in this corpus aims at CCK2 receptor (gastrin receptor) yet. Because it sits on the outside of the cell, it can be reached from the bloodstream: antibodies flag the cell, ADCs deliver a toxin, radioligands deliver radiation, and CAR-T or bispecifics bring a T cell.
External identifiers
Biology
A G-protein-coupled receptor for gastrin and cholecystokinin that physiologically regulates gastric acid secretion. It is overexpressed at very high density in medullary thyroid carcinoma and in a substantial minority of small-cell lung cancer, astrocytoma and other tumours, providing a target for minigastrin-based radiopeptides.
- Medullary thyroid carcinoma: expressed at high density in over 90% of cases
- Small-cell lung cancer: expressed in roughly half of cases
- Astrocytoma, stromal ovarian cancer, gastrointestinal stromal tumours, some gastroenteropancreatic neuroendocrine tumours: variable expression
- Normal gastric mucosa: physiological expression, the dose-limiting normal-tissue site for minigastrin therapy
Latest papers
topQuery for this target: (TITLE:"CCK2 receptor" OR ABSTRACT:"CCK2 receptor" OR TITLE:"gastrin receptor" OR ABSTRACT:"gastrin receptor" OR TITLE:"CCK2R" OR ABSTRACT:"CCK2R" OR TITLE:"CCK-B receptor" OR ABSTRACT:"CCK-B receptor") AND (radiopharmaceutical OR radioligand OR radionuclide OR theranostic OR "nuclear medicine" OR "molecular imaging" OR radiotracer OR scintigraphy OR cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about CCK2 receptor (gastrin receptor), not a curated reading list.
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