IRAK4 as a Radioligand Therapy Target
IRAK4, interleukin 1 receptor associated kinase 4, is a cell-surface protein (membrane receptor). In Human Protein Atlas immunohistochemistry, IRAK4 staining is highest in colorectal cancer (100% of samples positive), ovarian cancer (100% of samples positive) and endometrial cancer (100% of samples positive). Published literature reports that IRAK4 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Clinical-stage (up to phase 2, any modality).
Is IRAK4 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 colorectal 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.
IRAK4 expression in cancer
Protein expression of IRAK4 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 |
|---|---|---|---|
| Colorectal Cancer | 0.82 | High | 100% |
| Ovarian Cancer | 0.81 | High | 100% |
| Endometrial Cancer | 0.79 | High | 100% |
| Pancreatic Cancer | 0.70 | High | 100% |
| Breast Cancer | 0.69 | High | 100% |
| Neuroendocrine Tumors | 0.67 | High | 100% |
| Gastric Cancer | 0.67 | High | 100% |
| Cervical Cancer | 0.64 | High | 100% |
| Liver Cancer | 0.64 | High | 100% |
| Thyroid Cancer | 0.58 | High | 100% |
| Glioma | 0.58 | High | 100% |
| Head and Neck Cancer | 0.56 | High | 100% |
| Kidney Cancer | 0.48 | Medium | 91% |
| Skin Cancer | 0.48 | Medium | 82% |
| Lung Cancer | 0.43 | Medium | 90% |
| Prostate Cancer | 0.43 | Medium | 90% |
| Melanoma | 0.36 | Medium | 82% |
| Bladder Cancer | 0.30 | Medium | 82% |
| Testicular Cancer | 0.27 | Medium | 55% |
| Lymphoma | 0.25 | Medium | 50% |
Is IRAK4 internalized?
Yes. The IRAK4-targeting compounds also inhibited the kinase at single-digit μM concentrations in vitro, exhibited efficient internalization into HEK293H cells.
Sources: PMID 38033794 · PMID 32434410 · PMID 30522781 · PMID 29925372 · PMID 27224911. AI-extracted from abstracts, so verify before citing.
IRAK4 clinical trials
Clinical-stage (up to phase 2, any modality). Nuclens hasn't indexed trials for IRAK4 yet. Search ClinicalTrials.gov for IRAK4 trials.
IRAK4 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 IRAK4 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
IRAK4 gene essentiality (DepMap)
CRISPR knockout effect across 1258 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 colorectal cancer radioligand targets
c-MET (MET) · HER3 (ERBB3) · FAP · EGFR · CEA (CEACAM5) · EPCAM · SSTR2 · STEAP2
See all radioligand therapy targets in colorectal cancer.
See how IRAK4 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.