FAP as a Radioligand Therapy Target
FAP, fibroblast activation protein alpha, is a cell-surface protein. In Human Protein Atlas immunohistochemistry, FAP staining is highest in colorectal cancer (100% of samples positive), breast cancer (90% of samples positive) and pancreatic cancer (89% of samples positive). Published literature reports that FAP internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Clinical-stage (up to phase 3, any modality), with 5 active clinical trials.
Is FAP 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: 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.
FAP expression in cancer
Protein expression of FAP 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 | 0.80 | High | 100% |
| Breast Cancer | 0.77 | High | 90% |
| Pancreatic Cancer | 0.74 | High | 89% |
| Gastric Cancer | 0.70 | High | 100% |
| Prostate Cancer | 0.53 | High | 90% |
| Ovarian Cancer | 0.47 | Medium | 60% |
| Thyroid Cancer | 0.42 | Medium | 75% |
| Cervical Cancer | 0.41 | Medium | 56% |
| Bladder Cancer | 0.37 | Medium | 60% |
| Endometrial Cancer | 0.20 | Medium | 40% |
| Melanoma | 0.19 | Low | 42% |
| Head and Neck Cancer | 0.17 | Low | 50% |
| Neuroendocrine Tumors | 0.17 | Low | 25% |
| Liver Cancer | 0.15 | Low | 27% |
| Testicular Cancer | 0.14 | Low | 42% |
| Skin Cancer | 0.14 | Low | 25% |
| Lung Cancer | 0.12 | Low | 27% |
| Glioma | 0.08 | Low | 17% |
| Kidney Cancer | 0.03 | Low | 9% |
Not detected by IHC in: lymphoma.
Is FAP internalized?
Yes. This strategy effectively circumvents rapid efflux, dramatically prolongs intratumoral retention, and significantly enhances radiotherapeutic outcomes.
Sources: PMID 41813582 · PMID 41762411 · PMID 41666938 · PMID 41325906 · PMID 41105225. AI-extracted from abstracts, so verify before citing.
FAP clinical trials
Clinical-stage (up to phase 3, any modality). 5 active trials reference FAP (ClinicalTrials.gov, accessed 2026-09-21).
NCT07822347 · NCT07824479 · NCT04457258 · NCT07217704 · NCT07808177
FAP 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 FAP in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
FAP gene essentiality (DepMap)
CRISPR knockout effect across 1252 cancer cell lines: -0.00 (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) · EGFR · CEA (CEACAM5) · EPCAM · SSTR2 · STEAP2 · HER2 (ERBB2)
See all radioligand therapy targets in colorectal cancer.
See how FAP 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.