Mesothelin (MSLN) as a Radioligand Therapy Target
Mesothelin (MSLN), mesothelin, is a cell-surface protein. In Human Protein Atlas immunohistochemistry, Mesothelin staining is highest in pancreatic cancer (83% of samples positive), ovarian cancer (83% of samples positive) and gastric cancer (50% of samples positive). Published literature reports that Mesothelin internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Clinical-stage (up to phase 2, any modality), with 7 active clinical trials.
Is Mesothelin 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 pancreatic cancer, 83% of samples positive.
- ✅ Internalization: Reported to internalize, which favors radionuclide retention.
- ✅ Clinical precedent: Clinical-stage (up to phase 2, any modality)
- ❔ Shedding: Not yet assessed.
- ❔ Normal-tissue dosimetry: Check kidney, liver, bone marrow and salivary expression in the Human Protein Atlas tissue atlas.
Mesothelin expression in cancer
Protein expression of Mesothelin 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 |
|---|---|---|---|
| Pancreatic Cancer | 0.64 | High | 83% |
| Ovarian Cancer | 0.61 | High | 83% |
| Gastric Cancer | 0.33 | Medium | 50% |
| Cervical Cancer | 0.28 | Medium | 58% |
| Endometrial Cancer | 0.25 | Medium | 42% |
| Lung Cancer | 0.22 | Medium | 33% |
| Colorectal Cancer | 0.21 | Medium | 27% |
| Liver Cancer | 0.20 | Medium | 30% |
| Head and Neck Cancer | 0.17 | Low | 50% |
| Kidney Cancer | 0.15 | Low | 18% |
| Breast Cancer | 0.14 | Low | 17% |
| Testicular Cancer | 0.06 | Low | 8% |
| Skin Cancer | 0.03 | Low | 8% |
| Bladder Cancer | 0.03 | Low | 8% |
Not detected by IHC in: lymphoma, melanoma, thyroid cancer, neuroendocrine tumors, prostate cancer, glioma.
Is Mesothelin internalized?
Yes. The huCD39 mAb was internalized in a time-dependent manner.
Sources: PMID 39431011 · PMID 34577541 · PMID 29229273 · PMID 29059207. AI-extracted from abstracts, so verify before citing.
Mesothelin clinical trials
Clinical-stage (up to phase 2, any modality). 7 active trials reference Mesothelin (ClinicalTrials.gov, accessed 2026-06-29).
NCT06248697 · NCT06843629 · NCT07480928 · NCT07598955 · NCT05693844 · NCT07420010 · NCT07627711
Mesothelin 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 Mesothelin in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
Mesothelin gene essentiality (DepMap)
CRISPR knockout effect across 1251 cancer cell lines: 0.07 (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 pancreatic cancer radioligand targets
EGFR · HER3 (ERBB3) · c-MET (MET) · FAP · CEA (CEACAM5) · STEAP2 · SSTR2 · B7-H3 (CD276)
See all radioligand therapy targets in pancreatic cancer.
See how Mesothelin ranks against 15,000 targets for your indication.
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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.