FZD6 as a Radioligand Therapy Target
FZD6, frizzled class receptor 6, is a cell-surface protein (GPCR). In Human Protein Atlas immunohistochemistry, FZD6 staining is highest in cervical cancer (100% of samples positive), skin cancer (100% of samples positive) and colorectal cancer (100% of samples positive). Published literature reports that FZD6 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Discovery-stage (no clinical drug program).
Is FZD6 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 cervical 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.
FZD6 expression in cancer
Protein expression of FZD6 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 |
|---|---|---|---|
| Cervical Cancer | 0.94 | High | 100% |
| Skin Cancer | 0.94 | High | 100% |
| Colorectal Cancer | 0.92 | High | 100% |
| Head and Neck Cancer | 0.92 | High | 100% |
| Endometrial Cancer | 0.92 | High | 100% |
| Thyroid Cancer | 0.89 | High | 100% |
| Bladder Cancer | 0.88 | High | 100% |
| Testicular Cancer | 0.87 | High | 100% |
| Liver Cancer | 0.86 | High | 100% |
| Lung Cancer | 0.85 | High | 100% |
| Ovarian Cancer | 0.83 | High | 100% |
| Pancreatic Cancer | 0.77 | High | 100% |
| Breast Cancer | 0.72 | High | 100% |
| Kidney Cancer | 0.70 | High | 100% |
| Neuroendocrine Tumors | 0.67 | High | 100% |
| Gastric Cancer | 0.67 | High | 100% |
| Prostate Cancer | 0.64 | High | 100% |
| Melanoma | 0.63 | High | 100% |
| Glioma | 0.58 | High | 92% |
| Lymphoma | 0.24 | Medium | 55% |
Is FZD6 internalized?
Yes. RNF43 and ZNRF3 preferentially down-regulate specific FZDs, in part by a TMD-dependent mechanism, indicating endocytosis of FZD6.
Sources: PMID 38969364 · PMID 21743464 · PMID 18673242. AI-extracted from abstracts, so verify before citing.
FZD6 clinical trials
Discovery-stage (no clinical drug program). Nuclens hasn't indexed trials for FZD6 yet. Search ClinicalTrials.gov for FZD6 trials.
FZD6 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 FZD6 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
FZD6 gene essentiality (DepMap)
CRISPR knockout effect across 1258 cancer cell lines: 0.13 (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 cervical cancer radioligand targets
c-MET (MET) · EGFR · HER3 (ERBB3) · CEA (CEACAM5) · SSTR2 · Mesothelin (MSLN) · ITGB6 · STEAP2
See all radioligand therapy targets in cervical cancer.
See how FZD6 ranks against 15,000 targets for your indication.
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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.