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FAP (fibroblast activation protein) sits on the cancer-associated fibroblasts that scaffold more than 90% of epithelial cancers and is almost absent from normal adult tissue. FAPI PET tracers therefore light up tumours with high contrast, including pancreatic, gastric and low-grade cancers where FDG PET is weak, and FAP-targeted radioligands are in development.
Fibroblast activation protein is expressed on cancer-associated fibroblasts in >90% of epithelial cancers, with minimal expression in normal adult tissue. FAPI PET tracers (68Ga-FAPI-46, 18F-FAPI-74) offer high tumour-to-background contrast, including in cancers where FDG is weak (pancreatic, gastric, low-grade). FAP-targeted radioligands (177Lu/225Ac-FAP-2286) are in development.
In plain words · FAP (fibroblast activation protein) sits on the cancer-associated fibroblasts that scaffold more than 90% of epithelial cancers and is almost absent from normal adult tissue. FAPI PET tracers therefore light up tumours with high contrast, including pancreatic, gastric and low-grade cancers where FDG PET is weak, and FAP-targeted radioligands are in development.
FAP (fibroblast activation protein) sits on the cancer-associated fibroblasts that scaffold more than 90% of epithelial cancers and is almost absent from normal adult tissue. FAPI PET tracers therefore light up tumours with high contrast, including pancreatic, gastric and low-grade cancers where FDG PET is weak, and FAP-targeted radioligands are in development.
Serine protease on activated fibroblasts; a stromal target rather than a tumour-cell target, so it is pan-cancer but does not report on the malignant cell itself.
2 products aim at FAP: bispecific antibodies and radioligands. The target is on the supporting tissue around the tumour, so drugs aim to breach the wall or use it as a beacon for radioligands and imaging.
Immune or microenvironment target: the record's class is stroma. HPA FAP: RNA tissue enhanced (endometrium 1 29 nTPM); no normal tissue stained high; highest cancer staining breast cancer (6 of 10 high). Distribution: 4 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Pancreatic ductal adenocarcinoma, Gastric & gastro-oesophageal junction cancer, Breast cancer (all types), Sarcomas (soft tissue, bone, GIST)); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 1 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas FAP tissue; UniProt Q12884; Open Targets ENSG00000078098 associations
First described 1994. Earliest sequence paper UniProt cites for the protein: Scanlan M.J. et al, Proc. Natl. Acad. Sci. U.S.A, 1994, "Molecular cloning of fibroblast activation protein alpha, a member of the serine protease family selectively expressed in stromal fibroblasts of epithelial cancers". Source.
Serine protease on activated fibroblasts; a stromal target rather than a tumour-cell target, so it is pan-cancer but does not report on the malignant cell itself.
RNA: tissue enhanced (endometrium 1 29 nTPM), detected in many normal tissues.
No normal tissue stained high.
Medium only: carcinoid, endometrial cancer, glioma, liver cancer.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Pancreatic ductal adenocarcinoma | >90% | Stromal FAP by IHC/FAPI PET | Cancer-associated fibroblasts | Wikipedia |
| Gastric & gastro-oesophageal junction cancer | >85% | Stromal FAP | Wikipedia | |
| Triple-negative breast cancer | >80% | Stromal FAP | Wikipedia | |
| Sarcomas | 60-90% | Tumour and stromal FAP | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
EB-MF-CAR-NK-01 is an experimental bispecific antibody from Beijing Biotech in phase 2 trials for mesothelioma, aimed at Mesothelin and FAP.
A FAP-targeted theranostic pair: one version images almost any solid tumour, the other treats it with radiation.
The myCAF and iCAF distinction is why 'target the stroma' became 'target a fibroblast state', and IL-6 blockade combinations follow from it.
Together with the negative HALO-301 trial of hyaluronidase this ended the first, blunt version of stromal targeting; second-generation ideas aim to reprogramme rather than remove the stroma.
The mechanistic account of T-cell exclusion that all later combination immunotherapy trials in pancreatic cancer cite, and the origin of CXCR4 inhibitor combinations.
Query for this target: (TITLE:"FAP" OR ABSTRACT:"FAP") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about FAP, not a curated reading list.
Shares Uwe Haberkorn, Ken Herrmann, University Hospital Düsseldorf / CIO Düsseldorf, Heidelberg University Hospital / NCT / DKFZ and the tags theranostic, pet-target.
Shares Radioligand therapy (beta emitters) and the tag theranostic.
Shares Targeted alpha therapy, Radioligand therapy (beta emitters) and the tag theranostic.
Shares Reprogramme the stroma rather than remove it: second-generation stromal trials with a stromal biomarker and a survival endpoint, Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival, Mechanical theory: stiffness, pressure and force as causes, Desmoplasia (tumour stroma).
Shares Shaoli Song, Triple-negative breast cancer (TNBC) and the tag pet-target.
Shares Cancer-associated fibroblasts (CAFs), Reprogramme the stroma rather than remove it: second-generation stromal trials with a stromal biomarker and a survival endpoint, Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival, Desmoplasia (tumour stroma).
Shares Frederik Giesel, Uwe Haberkorn, FAP theranostics as a pan-cancer stromal strategy, Heidelberg University Hospital / NCT / DKFZ.
Shares Frederik Giesel, Uwe Haberkorn, Ken Herrmann, Heidelberg University Hospital / NCT / DKFZ.