Fibroblast activation protein alpha: Comprehensive detection methods for drug target and tumor marker

Fibroblast activation protein alpha (FAP-α, EC3.4.2. B28), a type II transmembrane proteolytic enzyme for the serine protease peptidase family. It is underexpressed in normal tissues but increased significantly in disease states, especially in neoplasm, which is a potential biomarker to turmor diagnosis. The inhibition of FAP-α activity will retard tumor formation, which is expected to be a promising tumor therapeutic target. At present, although the FAP-α expression detection methods has diversification, a superlative detection means is necessary for the clinical diagnosis. This review covers the discovery and the latest advances in FAP-α, as well as the future research prospects. The tissue distribution, structural characteristics, small-molecule ligands and structure-activity relationship of major inhibitors of FAP-α were summarized in this review. Furthermore, a variety of detection methods including traditional detection methods and emerging probes detection were classified and compared, and the design strategy and kinetic parameters of these FAP-α probe substrates were summarized. In addition, these comprehensive information provides a series of practical and reliable assays for the optimal design principles of FAP-α probes, promoting the application of FAP-α as a disease marker in diagnosis, and a drug target in drug design.