Targeting fibroblast activation protein in cancer - Prospects and caveats
Language English Country Singapore Media electronic
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
PubMed
29772538
DOI
10.2741/4682
PII: 4682
Knihovny.cz E-resources
- MeSH
- Molecular Targeted Therapy methods MeSH
- Endopeptidases MeSH
- Enzyme Inhibitors therapeutic use MeSH
- Humans MeSH
- Membrane Proteins antagonists & inhibitors genetics metabolism MeSH
- Tumor Microenvironment drug effects genetics MeSH
- Neoplasms drug therapy genetics metabolism MeSH
- Gene Expression Regulation, Enzymologic drug effects MeSH
- Gene Expression Regulation, Neoplastic drug effects MeSH
- Serine Endopeptidases genetics metabolism MeSH
- Gelatinases antagonists & inhibitors genetics metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Endopeptidases MeSH
- fibroblast activation protein alpha MeSH Browser
- Enzyme Inhibitors MeSH
- Membrane Proteins MeSH
- Serine Endopeptidases MeSH
- Gelatinases MeSH
Fibroblast activation protein (FAP, seprase) is a serine protease with post-proline dipeptidyl peptidase and endopeptidase enzymatic activity. FAP is upregulated in several tumor types, while its expression in healthy adult tissues is scarce. FAP molecule itself and FAP+ stromal cells play an important although probably context-dependent and tumor type-specific pathogenetic role in tumor progression. We provide an overview of FAP expression under both physiological and pathological conditions with focus on human malignancies. We also review and critically analyze the results of studies which used various strategies for the therapeutic targeting of FAP including the use of low molecular weight inhibitors, FAP activated prodrugs, anti-FAP antibodies and their conjugates, FAP-CAR T cells, and FAP vaccines. A unique enzymatic activity and selective expression in tumor microenvironment make FAP a promising therapeutic target. A better understanding of its role in individual tumor types, careful selection of patients, and identification of suitable combinations with currently available anticancer treatments will be critical for a successful translation of preclinically tested approaches of FAP targeting into clinical setting.
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