AGER as a Radioligand Therapy Target
AGER, advanced glycosylation end-product specific receptor, is a cell-surface protein (membrane receptor). In Human Protein Atlas immunohistochemistry, AGER staining is highest in neuroendocrine tumors (25% of samples positive), testicular cancer (20% of samples positive) and bladder cancer (25% of samples positive). Published literature reports that AGER internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Clinical-stage (up to phase 3, any modality).
Is AGER 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: Low IHC staining in neuroendocrine tumors, 25% 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.
AGER expression in cancer
Protein expression of AGER 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 |
|---|---|---|---|
| Neuroendocrine Tumors | 0.17 | Low | 25% |
| Testicular Cancer | 0.13 | Low | 20% |
| Bladder Cancer | 0.11 | Low | 25% |
| Prostate Cancer | 0.09 | Low | 9% |
| Liver Cancer | 0.03 | Low | 9% |
| Kidney Cancer | 0.03 | Low | 8% |
Not detected by IHC in: skin cancer, colorectal cancer, head and neck cancer, ovarian cancer, lymphoma, breast cancer, melanoma, thyroid cancer, cervical cancer, lung cancer, pancreatic cancer, gastric cancer, endometrial cancer, glioma.
Is AGER internalized?
Yes. The study indicates that AGER mediates macropinocytosis, which facilitates the internalization of serum albumin, suggesting receptor internalization.
Sources: PMID 39879317 · PMID 32612147 · PMID 11024005 · PMID 8529130. AI-extracted from abstracts, so verify before citing.
AGER clinical trials
Clinical-stage (up to phase 3, any modality). Nuclens hasn't indexed trials for AGER yet. Search ClinicalTrials.gov for AGER trials.
AGER 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 AGER in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
AGER gene essentiality (DepMap)
CRISPR knockout effect across 1258 cancer cell lines: 0.12 (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 neuroendocrine tumors radioligand targets
HER3 (ERBB3) · c-MET (MET) · SSTR2 · STEAP2 · EPCAM · ITGB6 · KIT · FAP
See all radioligand therapy targets in neuroendocrine tumors.
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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.