HTR6 as a Radioligand Therapy Target
HTR6, 5-hydroxytryptamine receptor 6, is a cell-surface protein (GPCR). In Human Protein Atlas immunohistochemistry, HTR6 staining is highest in thyroid cancer (100% of samples positive), neuroendocrine tumors (100% of samples positive) and breast cancer (90% of samples positive). Published literature reports that HTR6 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Clinical-stage (up to phase 3, any modality).
Is HTR6 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 thyroid cancer, 100% 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.
HTR6 expression in cancer
Protein expression of HTR6 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 | 0.58 | High | 100% |
| Neuroendocrine Tumors | 0.58 | High | 100% |
| Breast Cancer | 0.47 | Medium | 90% |
| Liver Cancer | 0.46 | Medium | 100% |
| Kidney Cancer | 0.42 | Medium | 91% |
| Prostate Cancer | 0.41 | Medium | 100% |
| Testicular Cancer | 0.39 | Medium | 100% |
| Gastric Cancer | 0.28 | Medium | 58% |
| Colorectal Cancer | 0.27 | Medium | 70% |
| Pancreatic Cancer | 0.23 | Medium | 40% |
| Ovarian Cancer | 0.22 | Medium | 58% |
| Lung Cancer | 0.15 | Low | 36% |
| Bladder Cancer | 0.13 | Low | 40% |
| Cervical Cancer | 0.09 | Low | 27% |
| Head and Neck Cancer | 0.08 | Low | 25% |
| Melanoma | 0.06 | Low | 17% |
| Endometrial Cancer | 0.06 | Low | 17% |
Not detected by IHC in: skin cancer, lymphoma, glioma.
Is HTR6 internalized?
Yes. more than half of membrane-embedded G protein-coupled receptors (SSTR3 and HTR6) use RAB8A-regulated vesicles to transport into and inside primary cilia.
Sources: PMID 36857170 · PMID 25795301. AI-extracted from abstracts, so verify before citing.
HTR6 clinical trials
Clinical-stage (up to phase 3, any modality). Nuclens hasn't indexed trials for HTR6 yet. Search ClinicalTrials.gov for HTR6 trials.
HTR6 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 HTR6 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
HTR6 gene essentiality (DepMap)
CRISPR knockout effect across 1253 cancer cell lines: 0.06 (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 thyroid cancer radioligand targets
c-MET (MET) · HER3 (ERBB3) · EPCAM · SSTR2 · EGFR · ITGAV · STEAP2 · FAP
See all radioligand therapy targets in thyroid 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.