targetsTarget

FAP

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.

FAP: what it is and how drugs act on it · animated schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

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.

1 · What it is
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.
2 · What goes wrong in cancer
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.
3 · How drugs use it
3 products aim at FAP: radioligands and imaging agents. 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.

External identifiers

FAPHGNCEnsemblUniProtAlphaFold DBChEMBLOpen TargetsCIViCOncoKBCOSMICcBioPortalDepMapHuman Protein AtlasNCBI GeneOMIM

Biology

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.

Where it is found

Pancreatic
Gastric
Breast
Sarcoma
Almost all desmoplastic tumours

Class

stroma · FAP

Identifiers

HGNC HGNC:3590Ensembl ENSG00000078098UniProt Q12884NCBI Gene 2191

Products

3top

Phase 2Theranostic pair (peptide radioligand)

FAP-2286 (177Lu / 68Ga)

A FAP-targeted theranostic pair: one version images almost any solid tumour, the other treats it with radiation.

Phase 2PET tracer

Gallium-68 FAPI-46

An experimental PET tracer that lights up the scaffolding cells cancers build around themselves, not the cancer cells directly. It is still being tested, not yet an approved medicine.

Phase 1Alpha-emitting radioligand (FAP-alpha targeted)

Lead-212 PSV359

A drug that homes to the scaffolding cells tumours build around themselves, carrying a radioactive metal that fires alpha particles over a very short range. A matching scan version shows first whether a patient's tumour has the target.