HRH4 as a Radioligand Therapy Target
HRH4, histamine receptor H4, is a cell-surface protein (GPCR). In Human Protein Atlas immunohistochemistry, HRH4 staining is highest in head and neck cancer (100% of samples positive), ovarian cancer (100% of samples positive) and neuroendocrine tumors (100% of samples positive). Published literature reports that HRH4 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Clinical-stage (up to phase 2, any modality).
Is HRH4 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 head and neck cancer, 100% of samples positive.
- ✅ Internalization: Reported to internalize, which favors radionuclide retention.
- ✅ Clinical precedent: Clinical-stage (up to phase 2, any modality)
- ❔ Shedding: Not yet assessed.
- ❔ Normal-tissue dosimetry: Check kidney, liver, bone marrow and salivary expression in the Human Protein Atlas tissue atlas.
HRH4 expression in cancer
Protein expression of HRH4 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 |
|---|---|---|---|
| Head and Neck Cancer | 0.75 | High | 100% |
| Ovarian Cancer | 0.75 | High | 100% |
| Neuroendocrine Tumors | 0.75 | High | 100% |
| Endometrial Cancer | 0.73 | High | 100% |
| Colorectal Cancer | 0.72 | High | 100% |
| Bladder Cancer | 0.70 | High | 100% |
| Pancreatic Cancer | 0.70 | High | 100% |
| Breast Cancer | 0.67 | High | 100% |
| Melanoma | 0.67 | High | 100% |
| Thyroid Cancer | 0.67 | High | 100% |
| Cervical Cancer | 0.67 | High | 100% |
| Skin Cancer | 0.64 | High | 100% |
| Gastric Cancer | 0.61 | High | 100% |
| Lung Cancer | 0.61 | High | 91% |
| Testicular Cancer | 0.58 | High | 100% |
| Liver Cancer | 0.47 | Medium | 90% |
| Glioma | 0.46 | Medium | 82% |
| Prostate Cancer | 0.44 | Medium | 92% |
| Lymphoma | 0.39 | Medium | 73% |
| Kidney Cancer | 0.39 | Medium | 75% |
Is HRH4 internalized?
Yes. H4 R agonist at nanomolar levels led to a rapid internalization of H4 Rs.
Sources: PMID 25207698. AI-extracted from abstracts, so verify before citing.
HRH4 clinical trials
Clinical-stage (up to phase 2, any modality). Nuclens hasn't indexed trials for HRH4 yet. Search ClinicalTrials.gov for HRH4 trials.
HRH4 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 HRH4 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
HRH4 gene essentiality (DepMap)
CRISPR knockout effect across 1247 cancer cell lines: 0.02 (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 head and neck cancer radioligand targets
EGFR · c-MET (MET) · HER3 (ERBB3) · ITGAV · SSTR2 · B7-H3 (CD276) · STEAP2 · Mesothelin (MSLN)
See all radioligand therapy targets in head and neck cancer.
See how HRH4 ranks against 15,000 targets for your indication.
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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.