LEPR as a Radioligand Therapy Target
LEPR, leptin receptor, is a cell-surface protein (membrane receptor). In Human Protein Atlas immunohistochemistry, LEPR staining is highest in prostate cancer (10% of samples positive). Published literature reports that LEPR internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Clinical-stage (up to phase 3, any modality).
Is LEPR 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 prostate cancer, 10% 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.
LEPR expression in cancer
Protein expression of LEPR 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 |
|---|---|---|---|
| Prostate Cancer | 0.03 | Low | 10% |
Not detected by IHC in: skin cancer, colorectal cancer, head and neck cancer, ovarian cancer, lymphoma, breast cancer, melanoma, kidney cancer, thyroid cancer, bladder cancer, neuroendocrine tumors, cervical cancer, lung cancer, pancreatic cancer, gastric cancer, testicular cancer, endometrial cancer, glioma, liver cancer.
Is LEPR internalized?
Yes. HS regulated LepR expression and internalization, as treatment with HS-degrading enzymes decreased cell surface LepR.
Sources: PMID 39384005 · PMID 33772019 · PMID 25448064 · PMID 15131016. AI-extracted from abstracts, so verify before citing.
LEPR clinical trials
Clinical-stage (up to phase 3, any modality). Nuclens hasn't indexed trials for LEPR yet. Search ClinicalTrials.gov for LEPR trials.
LEPR 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 LEPR in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
LEPR gene essentiality (DepMap)
CRISPR knockout effect across 1258 cancer cell lines: -0.08 (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 prostate cancer radioligand targets
PSMA (FOLH1) · HER3 (ERBB3) · c-MET (MET) · EGFR · EPCAM · FAP · B7-H3 (CD276) · STEAP2
See all radioligand therapy targets in prostate cancer.
See how LEPR ranks against 15,000 targets for your indication.
Run a free analysisData sources
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.