GRK2 as a Radioligand Therapy Target
GRK2, G protein-coupled receptor kinase 2, is a cell-surface protein (GPCR). In Human Protein Atlas immunohistochemistry, GRK2 staining is highest in prostate cancer (100% of samples positive), lymphoma (92% of samples positive) and colorectal cancer (82% of samples positive). Published literature reports that GRK2 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Discovery-stage (no clinical drug program).
Is GRK2 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 prostate cancer, 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.
GRK2 expression in cancer
Protein expression of GRK2 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 |
|---|---|---|---|
| Prostate Cancer | 0.67 | High | 100% |
| Lymphoma | 0.67 | High | 92% |
| Colorectal Cancer | 0.64 | High | 82% |
| Bladder Cancer | 0.55 | High | 82% |
| Breast Cancer | 0.53 | High | 92% |
| Endometrial Cancer | 0.52 | High | 82% |
| Gastric Cancer | 0.50 | Medium | 80% |
| Pancreatic Cancer | 0.47 | Medium | 80% |
| Ovarian Cancer | 0.42 | Medium | 64% |
| Cervical Cancer | 0.36 | Medium | 67% |
| Head and Neck Cancer | 0.33 | Medium | 75% |
| Thyroid Cancer | 0.33 | Medium | 75% |
| Neuroendocrine Tumors | 0.33 | Medium | 50% |
| Testicular Cancer | 0.30 | Medium | 64% |
| Liver Cancer | 0.30 | Medium | 46% |
| Skin Cancer | 0.24 | Medium | 55% |
| Lung Cancer | 0.19 | Low | 33% |
| Glioma | 0.18 | Low | 36% |
| Kidney Cancer | 0.17 | Low | 42% |
| Melanoma | 0.17 | Low | 33% |
Is GRK2 internalized?
Yes. Increasing MOR density, co-expressing other class A GPCRs, or elevating GRK2 or β-arrestin abundance rescues agonist-induced MOR trafficking.
Sources: PMID 42124644 · PMID 41882347 · PMID 41827890 · PMID 41560294 · PMID 41552710. AI-extracted from abstracts, so verify before citing.
GRK2 clinical trials
Discovery-stage (no clinical drug program). Nuclens hasn't indexed trials for GRK2 yet. Search ClinicalTrials.gov for GRK2 trials.
GRK2 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 GRK2 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
GRK2 gene essentiality (DepMap)
CRISPR knockout effect across 1258 cancer cell lines: -0.19 (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 prostate cancer radioligand targets
PSMA (FOLH1) · HER3 (ERBB3) · c-MET (MET) · EGFR · EPCAM · FAP · B7-H3 (CD276) · STEAP2
See all radioligand therapy targets in prostate 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.