GFRA1 as a Radioligand Therapy Target
GFRA1, GDNF family receptor alpha 1, is a cell-surface protein (membrane receptor). In Human Protein Atlas immunohistochemistry, GFRA1 staining is highest in prostate cancer (82% of samples positive), breast cancer (58% of samples positive) and liver cancer (55% of samples positive). Published literature reports that GFRA1 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Discovery-stage (no clinical drug program).
Is GFRA1 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: Medium IHC staining in prostate cancer, 82% 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.
GFRA1 expression in cancer
Protein expression of GFRA1 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 |
|---|---|---|---|
| Prostate Cancer | 0.46 | Medium | 82% |
| Breast Cancer | 0.39 | Medium | 58% |
| Liver Cancer | 0.36 | Medium | 55% |
| Colorectal Cancer | 0.33 | Medium | 58% |
| Thyroid Cancer | 0.33 | Medium | 50% |
| Melanoma | 0.28 | Medium | 50% |
| Gastric Cancer | 0.27 | Medium | 40% |
| Head and Neck Cancer | 0.25 | Medium | 50% |
| Endometrial Cancer | 0.21 | Medium | 36% |
| Ovarian Cancer | 0.19 | Low | 33% |
| Cervical Cancer | 0.15 | Low | 36% |
| Lung Cancer | 0.15 | Low | 36% |
| Pancreatic Cancer | 0.15 | Low | 22% |
| Neuroendocrine Tumors | 0.08 | Low | 25% |
| Bladder Cancer | 0.06 | Low | 18% |
| Kidney Cancer | 0.06 | Low | 9% |
| Glioma | 0.06 | Low | 17% |
| Testicular Cancer | 0.03 | Low | 9% |
| Skin Cancer | 0.03 | Low | 8% |
Not detected by IHC in: lymphoma.
Is GFRA1 internalized?
Yes. The rapid internalization kinetics of GFRA1 makes it an ideal target for therapeutic exploitation as an antibody-drug conjugate (ADC).
Sources: PMID 29796165. AI-extracted from abstracts, so verify before citing.
GFRA1 clinical trials
Discovery-stage (no clinical drug program). Nuclens hasn't indexed trials for GFRA1 yet. Search ClinicalTrials.gov for GFRA1 trials.
GFRA1 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 GFRA1 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
GFRA1 gene essentiality (DepMap)
CRISPR knockout effect across 1252 cancer cell lines: 0.01 (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 prostate cancer radioligand targets
PSMA (FOLH1) · HER3 (ERBB3) · c-MET (MET) · EGFR · EPCAM · FAP · B7-H3 (CD276) · STEAP2
See all radioligand therapy targets in prostate 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.