GPER1 as a Radioligand Therapy Target
GPER1, G protein-coupled estrogen receptor 1, is a cell-surface protein (GPCR). In Human Protein Atlas immunohistochemistry, GPER1 staining is highest in colorectal cancer (100% of samples positive), testicular cancer (92% of samples positive) and lymphoma (83% of samples positive). Published literature reports that GPER1 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Discovery-stage (no clinical drug program).
Is GPER1 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, 100% 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.
GPER1 expression in cancer
Protein expression of GPER1 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 | 0.83 | High | 100% |
| Testicular Cancer | 0.78 | High | 92% |
| Lymphoma | 0.78 | High | 83% |
| Breast Cancer | 0.67 | High | 92% |
| Endometrial Cancer | 0.67 | High | 90% |
| Liver Cancer | 0.53 | High | 75% |
| Skin Cancer | 0.52 | High | 82% |
| Thyroid Cancer | 0.50 | Medium | 75% |
| Bladder Cancer | 0.42 | Medium | 83% |
| Pancreatic Cancer | 0.40 | Medium | 60% |
| Gastric Cancer | 0.36 | Medium | 75% |
| Head and Neck Cancer | 0.33 | Medium | 100% |
| Ovarian Cancer | 0.33 | Medium | 60% |
| Neuroendocrine Tumors | 0.33 | Medium | 50% |
| Cervical Cancer | 0.33 | Medium | 50% |
| Melanoma | 0.17 | Low | 25% |
| Lung Cancer | 0.10 | Low | 20% |
| Glioma | 0.07 | Low | 10% |
| Prostate Cancer | 0.06 | Low | 17% |
Not detected by IHC in: kidney cancer.
Is GPER1 internalized?
Yes. This study demonstrates that GPR30 couples to the canonical Gq-phospholipase C pathway and is rapidly internalized upon continuous exposure to the agonists.
Sources: PMID 36400433 · PMID 29421611 · PMID 26391661. AI-extracted from abstracts, so verify before citing.
GPER1 clinical trials
Discovery-stage (no clinical drug program). Nuclens hasn't indexed trials for GPER1 yet. Search ClinicalTrials.gov for GPER1 trials.
GPER1 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 GPER1 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
GPER1 gene essentiality (DepMap)
CRISPR knockout effect across 1257 cancer cell lines: 0.07 (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.