NTRK2 as a Radioligand Therapy Target
NTRK2, neurotrophic receptor tyrosine kinase 2, is a cell-surface protein (RTK). In Human Protein Atlas immunohistochemistry, NTRK2 staining is highest in thyroid cancer (50% of samples positive), breast cancer (36% of samples positive) and glioma (27% of samples positive). Published literature reports that NTRK2 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Clinical-stage (up to phase 3, any modality).
Is NTRK2 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: Low IHC staining in thyroid cancer, 50% of samples positive.
- ✅ Internalization: Reported to internalize, which favors radionuclide retention.
- ✅ Clinical precedent: Clinical-stage (up to phase 3, any modality)
- ❔ Shedding: Not yet assessed.
- ❔ Normal-tissue dosimetry: Check kidney, liver, bone marrow and salivary expression in the Human Protein Atlas tissue atlas.
NTRK2 expression in cancer
Protein expression of NTRK2 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 |
|---|---|---|---|
| Thyroid Cancer | 0.17 | Low | 50% |
| Breast Cancer | 0.12 | Low | 36% |
| Glioma | 0.09 | Low | 27% |
| Bladder Cancer | 0.06 | Low | 18% |
| Gastric Cancer | 0.03 | Low | 9% |
| Kidney Cancer | 0.03 | Low | 8% |
| Pancreatic Cancer | 0.03 | Low | 8% |
| Prostate Cancer | 0.03 | Low | 8% |
Not detected by IHC in: skin cancer, colorectal cancer, head and neck cancer, ovarian cancer, lymphoma, melanoma, neuroendocrine tumors, cervical cancer, lung cancer, testicular cancer, endometrial cancer, liver cancer.
Is NTRK2 internalized?
Yes. The sentence states, 'the lifecycle of neurotrophins and their receptors have been characterised over the years, including the formation, endocytosis and trafficking of signalling-competent ligand-receptor complexes.' This indicates that NTRK2 undergoes internalization upon ligand binding.
Sources: PMID 32079660 · PMID 31631060 · PMID 25423262. AI-extracted from abstracts, so verify before citing.
NTRK2 clinical trials
Clinical-stage (up to phase 3, any modality). Nuclens hasn't indexed trials for NTRK2 yet. Search ClinicalTrials.gov for NTRK2 trials.
NTRK2 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 NTRK2 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
NTRK2 gene essentiality (DepMap)
CRISPR knockout effect across 1254 cancer cell lines: 0.11 (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.
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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.