GRK6 as a Radioligand Therapy Target
GRK6, G protein-coupled receptor kinase 6, is a cell-surface protein (GPCR). In Human Protein Atlas immunohistochemistry, GRK6 staining is highest in lymphoma (100% of samples positive), thyroid cancer (75% of samples positive) and melanoma (100% of samples positive). Published literature reports that GRK6 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Discovery-stage (no clinical drug program).
Is GRK6 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 lymphoma, 100% of samples positive.
- ✅ Internalization: Reported to internalize, which favors radionuclide retention.
- ⚠️ Clinical precedent: Discovery-stage (no clinical drug program)
- ❔ Shedding: Not yet assessed.
- ❔ Normal-tissue dosimetry: Check kidney, liver, bone marrow and salivary expression in the Human Protein Atlas tissue atlas.
GRK6 expression in cancer
Protein expression of GRK6 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 |
|---|---|---|---|
| Lymphoma | 0.75 | High | 100% |
| Thyroid Cancer | 0.75 | High | 75% |
| Melanoma | 0.67 | High | 100% |
| Colorectal Cancer | 0.64 | High | 100% |
| Glioma | 0.55 | High | 91% |
| Testicular Cancer | 0.53 | High | 90% |
| Head and Neck Cancer | 0.50 | Medium | 100% |
| Prostate Cancer | 0.40 | Medium | 60% |
| Breast Cancer | 0.33 | Medium | 67% |
| Ovarian Cancer | 0.33 | Medium | 58% |
| Liver Cancer | 0.33 | Medium | 50% |
| Pancreatic Cancer | 0.31 | Medium | 67% |
| Endometrial Cancer | 0.28 | Medium | 42% |
| Bladder Cancer | 0.24 | Medium | 36% |
| Gastric Cancer | 0.23 | Medium | 40% |
| Cervical Cancer | 0.21 | Medium | 36% |
| Neuroendocrine Tumors | 0.17 | Low | 50% |
| Lung Cancer | 0.12 | Low | 27% |
| Kidney Cancer | 0.11 | Low | 25% |
| Skin Cancer | 0.06 | Low | 18% |
Is GRK6 internalized?
Yes. We find that the receptor kinase GRK6 acts in parallel with GRK2 and GRK3 to trigger internalization, and that internalization uses a β-arrestin-independent pathway.
Sources: PMID 41882347 · PMID 38883814 · PMID 38349966 · PMID 37660910 · PMID 36451830. AI-extracted from abstracts, so verify before citing.
GRK6 clinical trials
Discovery-stage (no clinical drug program). Nuclens hasn't indexed trials for GRK6 yet. Search ClinicalTrials.gov for GRK6 trials.
GRK6 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 GRK6 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
GRK6 gene essentiality (DepMap)
CRISPR knockout effect across 1258 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.
Related lymphoma radioligand targets
c-MET (MET) · CD20 (MS4A1) · HER3 (ERBB3) · CD45 (PTPRC) · CD19 · SSTR2 · STEAP2 · CD22
See all radioligand therapy targets in lymphoma.
See how GRK6 ranks against 15,000 targets for your indication.
Run a free analysisData 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.