Radioligand Therapy Targets in Thyroid Cancer
We screened every cell-surface protein with tumor immunohistochemistry data in thyroid cancer (including medullary and differentiated thyroid cancer). 4,106 show detectable protein staining. Established and emerging radioligand targets expressed in thyroid cancer include EPCAM, c-MET (MET), ITGAV and STEAP2. Below, we rank every candidate by tumor expression, internalization and clinical maturity.
Established and emerging radioligand targets in thyroid cancer
Targets already pursued with radioligands or other targeted modalities that show protein expression in thyroid cancer:
| Target | IHC in thyroid cancer | % positive | Internalizes |
|---|---|---|---|
| EPCAM | High (1.00) | 100% | — |
| c-MET (MET) | High (0.83) | 100% | yes |
| ITGAV | High (0.83) | 100% | — |
| STEAP2 | High (0.75) | 100% | — |
| HER3 (ERBB3) | High (0.67) | 100% | yes |
| TMEFF2 | High (0.58) | 100% | — |
| SSTR2 | Medium (0.50) | 100% | yes |
| Nectin-4 (NECTIN4) | Medium (0.50) | 100% | no |
| B7-H3 (CD276) | Medium (0.42) | 100% | — |
| FAP | Medium (0.42) | 75% | yes |
| TROP2 (TACSTD2) | Medium (0.33) | 67% | uncertain |
| EGFR | Medium (0.33) | 50% | yes |
| CD38 | Low (0.08) | 25% | — |
| KIT | Low (0.08) | 25% | no |
| DLK1 | Low (0.08) | 25% | — |
Top cell-surface targets for thyroid cancer radioligand therapy
A data-driven screen of every protein annotated as cell-surface. It deliberately surfaces novel, unvalidated candidates, so confirm localization and expression before prioritizing any of them.
| # | Target | IHC in thyroid cancer | % positive | Internalizes | Clinical stage |
|---|---|---|---|---|---|
| 1 | PTPRB protein tyrosine phosphatase receptor type B | High (0.92) | 100% | yes | Clinical |
| 2 | S1PR1 sphingosine-1-phosphate receptor 1 | High (0.83) | 100% | yes | Clinical |
| 3 | EPHA4 EPH receptor A4 | High (1.00) | 100% | yes | Discovery |
| 4 | CYSLTR2 cysteinyl leukotriene receptor 2 | High (1.00) | 100% | yes | Discovery |
| 5 | c-MET (MET) MET proto-oncogene, receptor tyrosine kinase | High (0.83) | 100% | yes | Clinical |
| 6 | FLT4 fms related receptor tyrosine kinase 4 | High (0.67) | 100% | yes | Clinical |
| 7 | AMFR autocrine motility factor receptor | High (1.00) | 100% | yes | Discovery |
| 8 | GPR139 G protein-coupled receptor 139 | High (1.00) | 100% | yes | Discovery |
| 9 | CD3G CD3 gamma subunit of T-cell receptor complex | High (0.78) | 100% | yes | Clinical |
| 10 | IGF1R insulin like growth factor 1 receptor | High (0.75) | 100% | yes | Clinical |
| 11 | AGTRAP angiotensin II receptor associated protein | High (0.92) | 100% | yes | Discovery |
| 12 | TAAR1 trace amine associated receptor 1 | High (1.00) | 100% | uncertain | Clinical |
| 13 | CHRNA7 cholinergic receptor nicotinic alpha 7 subunit | High (0.75) | 100% | yes | Clinical |
| 14 | M6PR mannose-6-phosphate receptor, cation dependent | High (0.92) | 100% | yes | Discovery |
| 15 | FZD6 frizzled class receptor 6 | High (0.89) | 100% | yes | Discovery |
| 16 | FGFR1 fibroblast growth factor receptor 1 | High (0.67) | 100% | yes | Clinical |
| 17 | HER3 (ERBB3) erb-b2 receptor tyrosine kinase 3 | High (0.67) | 100% | yes | Clinical |
| 18 | NR3C2 nuclear receptor subfamily 3 group C member 2 | High (0.83) | 100% | uncertain | Clinical |
| 19 | MST1R macrophage stimulating 1 receptor | High (0.67) | 100% | yes | Clinical |
| 20 | ADRM1 ADRM1 26S proteasome ubiquitin receptor | High (1.00) | 100% | uncertain | Clinical |
| 21 | CHRM2 cholinergic receptor muscarinic 2 | High (0.92) | 100% | uncertain | Clinical |
| 22 | NOTCH3 notch receptor 3 | High (0.67) | 100% | yes | Clinical |
| 23 | IL1R2 interleukin 1 receptor type 2 | High (0.67) | 100% | yes | Discovery |
| 24 | HTR6 5-hydroxytryptamine receptor 6 | High (0.58) | 100% | yes | Clinical |
| 25 | FZD3 frizzled class receptor 3 | High (0.83) | 100% | yes | Discovery |
Internalizing receptors in thyroid cancer
Targets expressed in thyroid cancer that the literature reports internalize after ligand binding. Internalization traps the radionuclide inside the tumor cell, which matters most for β-emitters like 177Lu and for α-emitters like 225Ac:
PTPRB · S1PR1 · EPHA4 · CYSLTR2 · c-MET (MET) · FLT4 · AMFR · GPR139 · CD3G · IGF1R · AGTRAP · CHRNA7
Thyroid Cancer targets already in clinical development
Targets with a clinical-stage drug program (any modality) that are also expressed in thyroid cancer. Clinical precedent lowers development risk but usually means more competition:
PTPRB · S1PR1 · c-MET (MET) · FLT4 · CD3G · IGF1R · TAAR1 · CHRNA7 · FGFR1 · HER3 (ERBB3) · NR3C2 · MST1R
How these thyroid cancer targets are ranked
Candidates are limited to proteins annotated as cell-surface (UniProt via Open Targets), because a radioligand has to reach its target from circulation. They are ranked by Nuclens' radiopharmaceutical pre-screen: immunohistochemistry staining and patient-sample positivity in thyroid cancer, literature evidence of internalization and shedding, clinical maturity, and cancer association. It is a first-pass triage, not a substitute for wet-lab validation or dosimetry. For the full framework, see what makes a good radioligand therapy target and emerging radioligand targets beyond PSMA.
Rank thyroid cancer targets against your own criteria: isotope, organ limits, novelty.
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Data sources
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.