TNFRSF1A as a Radioligand Therapy Target
TNFRSF1A, TNF receptor superfamily member 1A, is a cell-surface protein (membrane receptor). In Human Protein Atlas immunohistochemistry, TNFRSF1A staining is highest in bladder cancer (100% of samples positive), cervical cancer (100% of samples positive) and breast cancer (83% of samples positive). Published literature reports that TNFRSF1A internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Clinical-stage (up to phase 1, any modality).
Is TNFRSF1A 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 bladder cancer, 100% of samples positive.
- ✅ Internalization: Reported to internalize, which favors radionuclide retention.
- ✅ Clinical precedent: Clinical-stage (up to phase 1, any modality)
- ❔ Shedding: Not yet assessed.
- ❔ Normal-tissue dosimetry: Check kidney, liver, bone marrow and salivary expression in the Human Protein Atlas tissue atlas.
TNFRSF1A expression in cancer
Protein expression of TNFRSF1A 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 |
|---|---|---|---|
| Bladder Cancer | 0.58 | High | 100% |
| Cervical Cancer | 0.58 | High | 100% |
| Breast Cancer | 0.56 | High | 83% |
| Ovarian Cancer | 0.55 | High | 100% |
| Testicular Cancer | 0.55 | High | 100% |
| Colorectal Cancer | 0.53 | High | 100% |
| Gastric Cancer | 0.53 | High | 92% |
| Prostate Cancer | 0.47 | Medium | 100% |
| Liver Cancer | 0.47 | Medium | 100% |
| Thyroid Cancer | 0.42 | Medium | 100% |
| Pancreatic Cancer | 0.42 | Medium | 100% |
| Endometrial Cancer | 0.39 | Medium | 100% |
| Lung Cancer | 0.33 | Medium | 92% |
| Head and Neck Cancer | 0.33 | Medium | 75% |
| Melanoma | 0.28 | Medium | 67% |
| Skin Cancer | 0.17 | Low | 50% |
| Glioma | 0.17 | Low | 50% |
| Lymphoma | 0.14 | Low | 42% |
| Neuroendocrine Tumors | 0.08 | Low | 25% |
| Kidney Cancer | 0.03 | Low | 8% |
Is TNFRSF1A internalized?
Yes. depletion of ESCRT components leads to endosomal accumulation of TNFRI and LTβR
Sources: PMID 30333141 · PMID 21459945 · PMID 17473511. AI-extracted from abstracts, so verify before citing.
TNFRSF1A clinical trials
Clinical-stage (up to phase 1, any modality). Nuclens hasn't indexed trials for TNFRSF1A yet. Search ClinicalTrials.gov for TNFRSF1A trials.
TNFRSF1A 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 TNFRSF1A in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
TNFRSF1A 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 bladder cancer radioligand targets
EGFR · HER3 (ERBB3) · c-MET (MET) · SSTR2 · ITGAV · HER2 (ERBB2) · B7-H3 (CD276) · FAP
See all radioligand therapy targets in bladder 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.