LGR5 as a Radioligand Therapy Target
LGR5, leucine rich repeat containing G protein-coupled receptor 5, is a cell-surface protein (GPCR). In Human Protein Atlas immunohistochemistry, LGR5 staining is highest in colorectal cancer (100% of samples positive), gastric cancer (83% of samples positive) and liver cancer (92% of samples positive). Evidence on whether LGR5 internalizes is mixed. Clinical status: Discovery-stage (no clinical drug program).
Is LGR5 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 colorectal cancer, 100% of samples positive.
- ⚠️ Internalization: Mixed evidence.
- ⚠️ 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.
LGR5 expression in cancer
Protein expression of LGR5 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 |
|---|---|---|---|
| Colorectal Cancer | 0.64 | High | 100% |
| Gastric Cancer | 0.58 | High | 83% |
| Liver Cancer | 0.50 | Medium | 92% |
| Pancreatic Cancer | 0.47 | Medium | 80% |
| Breast Cancer | 0.44 | Medium | 92% |
| Cervical Cancer | 0.39 | Medium | 55% |
| Ovarian Cancer | 0.33 | Medium | 58% |
| Endometrial Cancer | 0.27 | Medium | 73% |
| Head and Neck Cancer | 0.25 | Medium | 50% |
| Neuroendocrine Tumors | 0.25 | Medium | 50% |
| Bladder Cancer | 0.24 | Medium | 64% |
| Thyroid Cancer | 0.22 | Medium | 67% |
| Prostate Cancer | 0.20 | Medium | 50% |
| Kidney Cancer | 0.17 | Low | 42% |
| Melanoma | 0.15 | Low | 36% |
| Lung Cancer | 0.09 | Low | 18% |
| Testicular Cancer | 0.08 | Low | 17% |
| Skin Cancer | 0.07 | Low | 20% |
Not detected by IHC in: lymphoma, glioma.
Is LGR5 internalized?
Uncertain. The abstract does not provide specific information on whether LGR5 undergoes receptor internalization or endocytosis upon ligand/antibody binding. It discusses the development of antibody-drug conjugates (ADCs) without explicitly mentioning the internalization behavior of the targeted receptors.
Sources: PMID 42207299 · PMID 40427162 · PMID 38414530 · PMID 33001511 · PMID 30853556. AI-extracted from abstracts, so verify before citing.
LGR5 clinical trials
Discovery-stage (no clinical drug program). Nuclens hasn't indexed trials for LGR5 yet. Search ClinicalTrials.gov for LGR5 trials.
LGR5 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 LGR5 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
LGR5 gene essentiality (DepMap)
CRISPR knockout effect across 1253 cancer cell lines: -0.03 (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 colorectal cancer radioligand targets
c-MET (MET) · HER3 (ERBB3) · FAP · EGFR · CEA (CEACAM5) · EPCAM · SSTR2 · STEAP2
See all radioligand therapy targets in colorectal 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.