LIFR as a Radioligand Therapy Target
LIFR, LIF receptor subunit alpha, is a cell-surface protein (membrane receptor). In Human Protein Atlas immunohistochemistry, LIFR staining is highest in gastric cancer (100% of samples positive), liver cancer (100% of samples positive) and pancreatic cancer (100% of samples positive). Published literature reports that LIFR internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Discovery-stage (no clinical drug program).
Is LIFR 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 gastric 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.
LIFR expression in cancer
Protein expression of LIFR 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 |
|---|---|---|---|
| Gastric Cancer | 0.97 | High | 100% |
| Liver Cancer | 0.97 | High | 100% |
| Pancreatic Cancer | 0.88 | High | 100% |
| Colorectal Cancer | 0.80 | High | 100% |
| Cervical Cancer | 0.77 | High | 100% |
| Endometrial Cancer | 0.70 | High | 100% |
| Glioma | 0.69 | High | 92% |
| Thyroid Cancer | 0.67 | High | 100% |
| Neuroendocrine Tumors | 0.67 | High | 100% |
| Breast Cancer | 0.67 | High | 90% |
| Head and Neck Cancer | 0.67 | High | 75% |
| Kidney Cancer | 0.64 | High | 75% |
| Testicular Cancer | 0.61 | High | 91% |
| Lung Cancer | 0.58 | High | 82% |
| Bladder Cancer | 0.55 | High | 91% |
| Prostate Cancer | 0.52 | High | 82% |
| Skin Cancer | 0.47 | Medium | 67% |
| Ovarian Cancer | 0.44 | Medium | 67% |
| Melanoma | 0.28 | Medium | 50% |
| Lymphoma | 0.14 | Low | 33% |
Is LIFR internalized?
Yes. Stimulation of cells with CNTFR causes translocation of LIFR and gp130 into the lipid rafts, suggesting that LIFR is subject to receptor trafficking upon binding.
Sources: PMID 22306348 · PMID 17873291 · PMID 16036214 · PMID 10085222 · PMID 9852103. AI-extracted from abstracts, so verify before citing.
LIFR clinical trials
Discovery-stage (no clinical drug program). Nuclens hasn't indexed trials for LIFR yet. Search ClinicalTrials.gov for LIFR trials.
LIFR 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 LIFR in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
LIFR 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 gastric cancer radioligand targets
HER3 (ERBB3) · c-MET (MET) · FAP · EGFR · SSTR2 · CEA (CEACAM5) · Mesothelin (MSLN) · STEAP2
See all radioligand therapy targets in gastric 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.