IMR Press / FBL / Volume 23 / Issue 10 / DOI: 10.2741/4682

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Review

Targeting fibroblast activation protein in cancer – Prospects and caveats

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1 Laboratory of Cancer Cell Biology, Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague 2, U Nemocnice 5, 128 53, Czech Republic
Front. Biosci. (Landmark Ed) 2018, 23(10), 1933–1968; https://doi.org/10.2741/4682
Published: 1 June 2018
(This article belongs to the Special Issue Dipeptidyl peptidase IV and related molecules in health and disease)
Abstract

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.

Keywords
Stroma targeted therapy
Cancer associated fibroblasts
Cancer therapy
Tumor microenvironment
Protease
Seprase
Cancer immunosuppression
Review
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