Fibroblast activation protein alpha (FAP (or FAP-α))

Fibroblast activation protein alpha (FAP, also called FAP-α) is a type II transmembrane serine protease encoded by the FAP gene and expressed primarily on the surface of activated fibroblasts, especially cancer-associated fibroblasts (CAFs), during tissue remodeling, wound healing, fibrosis, and in most types of solid tumors but not in normal adult tissues[1][2][3][4][5][6][7]. FAP exhibits both dipeptidyl peptidase and endopeptidase activities, capable of degrading extracellular matrix components and processing bioactive peptides, contributing to tissue remodeling, tumor invasion, metastasis, angiogenesis, and immunosuppressive tumor microenvironment formation[1][2][3][5][7]. FAP is a clinically significant biomarker for CAFs and is considered an attractive therapeutic and imaging target in oncology, with radiolabeled inhibitor tracers (FAPI compounds) widely used in cancer diagnosis and the development of theranostic approaches[4][6]. Multiple experimental drugs inhibit FAP enzymatic activity or deliver toxins/radiation to FAP-expressing cells, although risks include disruption of normal tissue repair and unintended effects in non-malignant disease processes where FAP is also upregulated[7].

Other names

prolyl endopeptidase FAPsepraseFAP-αfibroblast activating proteinFAPαfibroblast activation protein, alpha

Enzyme inhibition (blocking proteolytic activity to suppress extracellular matrix remodeling, tumor cell invasion, and migration). Targeted radionuclide delivery (radioligand therapy by directly binding to FAP-expressing cells and delivering cytotoxic radiation). Imaging – using FAP-targeted tracers in PET/SPECT to visualize and characterize tumors based on fibroblast activity.