Radioligand Therapy Targets in Neuroendocrine Tumors
We screened every cell-surface protein with tumor immunohistochemistry data in neuroendocrine tumors (including carcinoid and gastroenteropancreatic neuroendocrine tumors (GEP-NETs)). 3,865 show detectable protein staining. Established and emerging radioligand targets expressed in neuroendocrine tumors include HER3 (ERBB3), c-MET (MET), STEAP2 and SSTR2. Below, we rank every candidate by tumor expression, internalization and clinical maturity.
Established and emerging radioligand targets in neuroendocrine tumors
Targets already pursued with radioligands or other targeted modalities that show protein expression in neuroendocrine tumors:
| Target | IHC in neuroendocrine tumors | % positive | Internalizes |
|---|---|---|---|
| HER3 (ERBB3) | High (0.75) | 100% | yes |
| c-MET (MET) | High (0.58) | 100% | yes |
| STEAP2 | High (0.58) | 100% | — |
| SSTR2 | Medium (0.50) | 100% | yes |
| EPCAM | Medium (0.50) | 75% | — |
| ITGB6 | Medium (0.42) | 100% | — |
| ITGAV | Medium (0.33) | 50% | — |
| TMEFF2 | Medium (0.33) | 50% | — |
| KIT | Medium (0.25) | 50% | no |
| B7-H3 (CD276) | Low (0.17) | 50% | — |
| FAP | Low (0.17) | 25% | yes |
| Nectin-4 (NECTIN4) | Low (0.08) | 25% | no |
| CD19 | Low (0.08) | 25% | — |
Top cell-surface targets for neuroendocrine tumors 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 neuroendocrine tumors | % positive | Internalizes | Clinical stage |
|---|---|---|---|---|---|
| 1 | NR3C2 nuclear receptor subfamily 3 group C member 2 | High (1.00) | 100% | uncertain | Clinical |
| 2 | IGF1R insulin like growth factor 1 receptor | High (0.83) | 100% | yes | Clinical |
| 3 | CYSLTR2 cysteinyl leukotriene receptor 2 | High (0.83) | 100% | yes | Discovery |
| 4 | AMFR autocrine motility factor receptor | High (1.00) | 100% | yes | Discovery |
| 5 | HER3 (ERBB3) erb-b2 receptor tyrosine kinase 3 | High (0.75) | 100% | yes | Clinical |
| 6 | PTPN13 protein tyrosine phosphatase non-receptor type 13 | High (0.92) | 100% | yes | Discovery |
| 7 | NOTCH3 notch receptor 3 | High (0.75) | 100% | yes | Clinical |
| 8 | PTPRB protein tyrosine phosphatase receptor type B | High (0.67) | 67% | yes | Clinical |
| 9 | HRH4 histamine receptor H4 | High (0.75) | 100% | yes | Clinical |
| 10 | c-MET (MET) MET proto-oncogene, receptor tyrosine kinase | High (0.58) | 100% | yes | Clinical |
| 11 | SV2A synaptic vesicle glycoprotein 2A | High (1.00) | 100% | — | Clinical |
| 12 | IL1R2 interleukin 1 receptor type 2 | High (0.67) | 100% | yes | Discovery |
| 13 | HTR6 5-hydroxytryptamine receptor 6 | High (0.58) | 100% | yes | Clinical |
| 14 | FZD3 frizzled class receptor 3 | High (0.83) | 100% | yes | Discovery |
| 15 | CHRNA7 cholinergic receptor nicotinic alpha 7 subunit | High (0.67) | 100% | yes | Clinical |
| 16 | GPR139 G protein-coupled receptor 139 | High (0.83) | 100% | yes | Discovery |
| 17 | ADGRL1 adhesion G protein-coupled receptor L1 | High (0.83) | 100% | yes | Discovery |
| 18 | BDKRB1 bradykinin receptor B1 | High (1.00) | 100% | uncertain | Clinical |
| 19 | IRAK4 interleukin 1 receptor associated kinase 4 | High (0.67) | 100% | yes | Clinical |
| 20 | MAOB monoamine oxidase B | High (0.92) | 100% | — | Clinical |
| 21 | FLT4 fms related receptor tyrosine kinase 4 | Medium (0.44) | 100% | yes | Clinical |
| 22 | FGFR1 fibroblast growth factor receptor 1 | High (0.58) | 100% | yes | Clinical |
| 23 | NOTCH1 notch receptor 1 | High (0.58) | 100% | yes | Clinical |
| 24 | ADRM1 ADRM1 26S proteasome ubiquitin receptor | High (0.92) | 100% | uncertain | Clinical |
| 25 | EPHB4 EPH receptor B4 | High (0.58) | 100% | yes | Clinical |
Internalizing receptors in neuroendocrine tumors
Targets expressed in neuroendocrine tumors 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:
IGF1R · CYSLTR2 · AMFR · HER3 (ERBB3) · PTPN13 · NOTCH3 · PTPRB · HRH4 · c-MET (MET) · IL1R2 · HTR6 · FZD3
Neuroendocrine Tumors targets already in clinical development
Targets with a clinical-stage drug program (any modality) that are also expressed in neuroendocrine tumors. Clinical precedent lowers development risk but usually means more competition:
NR3C2 · IGF1R · HER3 (ERBB3) · NOTCH3 · PTPRB · HRH4 · c-MET (MET) · SV2A · HTR6 · CHRNA7 · BDKRB1 · IRAK4
How these neuroendocrine tumors 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 neuroendocrine tumors, 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 neuroendocrine tumors 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.