GPR4 as a Radioligand Therapy Target
GPR4, G protein-coupled receptor 4, is a cell-surface protein (GPCR). In Human Protein Atlas immunohistochemistry, GPR4 staining is highest in colorectal cancer (90% of samples positive), breast cancer (91% of samples positive) and thyroid cancer (100% of samples positive). Published literature reports that GPR4 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Discovery-stage (no clinical drug program).
Is GPR4 a good radioligand therapy target?
Scored against the six criteria that decide whether a protein can become a radioligand therapy:
- ✅ Cell-surface accessibility: Localized to the cell surface, so a radioligand can reach it from circulation.
- ✅ Tumor expression: High IHC staining in colorectal cancer, 90% of samples positive.
- ✅ Internalization: Reported to internalize, which favors radionuclide retention.
- ⚠️ Clinical precedent: Discovery-stage (no clinical drug program)
- ❔ Shedding: Not yet assessed.
- ❔ Normal-tissue dosimetry: Check kidney, liver, bone marrow and salivary expression in the Human Protein Atlas tissue atlas.
GPR4 expression in cancer
Protein expression of GPR4 across 20 cancer types from Human Protein Atlas immunohistochemistry. The score is a weighted staining intensity from 0 to 1; "% positive" is the share of patient samples with detectable staining.
| Cancer type | IHC score | Level | % positive |
|---|---|---|---|
| Colorectal Cancer | 0.77 | High | 90% |
| Breast Cancer | 0.58 | High | 91% |
| Thyroid Cancer | 0.50 | Medium | 100% |
| Ovarian Cancer | 0.50 | Medium | 83% |
| Testicular Cancer | 0.48 | Medium | 100% |
| Endometrial Cancer | 0.48 | Medium | 82% |
| Lymphoma | 0.47 | Medium | 75% |
| Gastric Cancer | 0.46 | Medium | 82% |
| Melanoma | 0.44 | Medium | 92% |
| Glioma | 0.44 | Medium | 92% |
| Bladder Cancer | 0.42 | Medium | 82% |
| Liver Cancer | 0.42 | Medium | 82% |
| Prostate Cancer | 0.40 | Medium | 90% |
| Head and Neck Cancer | 0.33 | Medium | 75% |
| Cervical Cancer | 0.33 | Medium | 67% |
| Lung Cancer | 0.33 | Medium | 58% |
| Neuroendocrine Tumors | 0.33 | Medium | 50% |
| Pancreatic Cancer | 0.30 | Medium | 60% |
| Skin Cancer | 0.21 | Medium | 46% |
| Kidney Cancer | 0.14 | Low | 33% |
Is GPR4 internalized?
Yes. GPR4 internalization within GPR4-expressing cells were all inhibited by the GPR4 modulator.
Sources: PMID 26070068 · PMID 16291861 · PMID 14567679 · PMID 11535583. AI-extracted from abstracts, so verify before citing.
GPR4 clinical trials
Discovery-stage (no clinical drug program). Nuclens hasn't indexed trials for GPR4 yet. Search ClinicalTrials.gov for GPR4 trials.
GPR4 normal tissue expression
Normal-tissue expression in dose-limiting organs (kidney, liver, bone marrow, salivary glands) drives radioligand dosimetry risk. Nuclens is re-validating its normal-tissue values, so they are not shown here yet. See GPR4 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
GPR4 gene essentiality (DepMap)
CRISPR knockout effect across 1248 cancer cell lines: 0.04 (not essential). Radioligands kill by radiation, not by blocking the target, so essentiality matters less than for inhibitors. A non-essential target can still be an excellent radioligand target.
Related colorectal cancer radioligand targets
c-MET (MET) · HER3 (ERBB3) · FAP · EGFR · CEA (CEACAM5) · EPCAM · SSTR2 · STEAP2
See all radioligand therapy targets in colorectal cancer.
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Subcellular localization: UniProt via Open Targets (CC BY 4.0 / CC0). Tumor immunohistochemistry: Human Protein Atlas (CC BY-SA 4.0). Clinical trials: ClinicalTrials.gov (public domain). Gene essentiality: DepMap (CC BY 4.0). Internalization and shedding: AI-extracted from PubMed abstracts, so verify against the cited papers before relying on them. Nuclens is a first-pass triage layer, not a substitute for wet-lab validation or clinical dosimetry. Derived expression data on this page is shared under CC BY-SA 4.0.