CHRNA4 as a Radioligand Therapy Target
CHRNA4, cholinergic receptor nicotinic alpha 4 subunit, is a cell-surface protein (membrane receptor). In Human Protein Atlas immunohistochemistry, CHRNA4 staining is highest in thyroid cancer (100% of samples positive), liver cancer (100% of samples positive) and colorectal cancer (100% of samples positive). Evidence on whether CHRNA4 internalizes is mixed. Clinical status: Clinical-stage (up to phase 3, any modality).
Is CHRNA4 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 thyroid cancer, 100% of samples positive.
- ⚠️ Internalization: Mixed evidence.
- ✅ 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.
CHRNA4 expression in cancer
Protein expression of CHRNA4 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 |
|---|---|---|---|
| Thyroid Cancer | 0.58 | High | 100% |
| Liver Cancer | 0.58 | High | 100% |
| Colorectal Cancer | 0.58 | High | 100% |
| Gastric Cancer | 0.50 | Medium | 83% |
| Neuroendocrine Tumors | 0.50 | Medium | 75% |
| Pancreatic Cancer | 0.47 | Medium | 90% |
| Head and Neck Cancer | 0.42 | Medium | 100% |
| Endometrial Cancer | 0.33 | Medium | 82% |
| Testicular Cancer | 0.31 | Medium | 75% |
| Prostate Cancer | 0.27 | Medium | 60% |
| Cervical Cancer | 0.24 | Medium | 46% |
| Breast Cancer | 0.22 | Medium | 58% |
| Ovarian Cancer | 0.21 | Medium | 55% |
| Bladder Cancer | 0.21 | Medium | 36% |
| Kidney Cancer | 0.19 | Low | 50% |
| Melanoma | 0.18 | Low | 46% |
| Glioma | 0.17 | Low | 50% |
| Lung Cancer | 0.12 | Low | 18% |
| Lymphoma | 0.06 | Low | 18% |
| Skin Cancer | 0.03 | Low | 9% |
Is CHRNA4 internalized?
Uncertain. The abstract does not provide specific information regarding the internalization or endocytosis of the CHRNA4 protein upon ligand or antibody binding.
Sources: PMID 31294817. AI-extracted from abstracts, so verify before citing.
CHRNA4 clinical trials
Clinical-stage (up to phase 3, any modality). Nuclens hasn't indexed trials for CHRNA4 yet. Search ClinicalTrials.gov for CHRNA4 trials.
CHRNA4 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 CHRNA4 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
CHRNA4 gene essentiality (DepMap)
CRISPR knockout effect across 1235 cancer cell lines: -0.06 (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 thyroid cancer radioligand targets
c-MET (MET) · HER3 (ERBB3) · EPCAM · SSTR2 · EGFR · ITGAV · STEAP2 · FAP
See all radioligand therapy targets in thyroid 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.