FZD3 as a Radioligand Therapy Target
FZD3, frizzled class receptor 3, is a cell-surface protein (GPCR). In Human Protein Atlas immunohistochemistry, FZD3 staining is highest in colorectal cancer (100% of samples positive), testicular cancer (100% of samples positive) and head and neck cancer (100% of samples positive). Published literature reports that FZD3 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Discovery-stage (no clinical drug program).
Is FZD3 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.
FZD3 expression in cancer
Protein expression of FZD3 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 | 0.97 | High | 100% |
| Testicular Cancer | 0.85 | High | 100% |
| Head and Neck Cancer | 0.83 | High | 100% |
| Thyroid Cancer | 0.83 | High | 100% |
| Neuroendocrine Tumors | 0.83 | High | 100% |
| Bladder Cancer | 0.81 | High | 100% |
| Liver Cancer | 0.81 | High | 100% |
| Lung Cancer | 0.80 | High | 100% |
| Gastric Cancer | 0.79 | High | 100% |
| Endometrial Cancer | 0.79 | High | 100% |
| Pancreatic Cancer | 0.76 | High | 91% |
| Prostate Cancer | 0.75 | High | 100% |
| Ovarian Cancer | 0.72 | High | 100% |
| Kidney Cancer | 0.69 | High | 100% |
| Skin Cancer | 0.67 | High | 100% |
| Melanoma | 0.64 | High | 100% |
| Breast Cancer | 0.63 | High | 100% |
| Cervical Cancer | 0.56 | High | 83% |
| Glioma | 0.53 | High | 90% |
| Lymphoma | 0.47 | Medium | 92% |
Is FZD3 internalized?
Yes. FZD3, along with other FZD receptors, transduces WNT signals based on ligand-dependent preferentiality for caveolin- or clathrin-mediated endocytosis.
Sources: PMID 18673242. AI-extracted from abstracts, so verify before citing.
FZD3 clinical trials
Discovery-stage (no clinical drug program). Nuclens hasn't indexed trials for FZD3 yet. Search ClinicalTrials.gov for FZD3 trials.
FZD3 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 FZD3 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
FZD3 gene essentiality (DepMap)
CRISPR knockout effect across 1258 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 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.