Cited by 102Cell death mechanisms and regulationCancer-related Molecular PathwaysToxin Mechanisms and Immunotoxins

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Protein-based therapeutic approaches targeting death receptors

French, Lars E, Tschopp, Jürg·2003·Cell Death & Differentiation

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Abstract

Death receptors (DRs) are a growing family of transmembrane proteins that can detect the presence of specific extracellular death signals and rapidly trigger cellular destruction by apoptosis. Eight human DRs (Fas, TNF-R1, TRAMP, TRAIL-R1, TRAIL-R2, DR-6, EDA-R and NGF-R) have been identified. The best studied to date is Fas (CD95). Expression and signaling by Fas and its ligand (FasL, CD95L) is a tightly regulated process essential for key physiological functions in a variety of organs, including the maintenance of immune homeostasis. Recently, strong evidence has shown that dysregulation of Fas expression and/or signaling contributes to the pathogenesis of tissue destructive diseases such as graft-versus-host disease, toxic epidermal necrolysis, multiple sclerosis and stroke. With these new developments, strategies for modulating the function of Fas signaling have emerged and provided novel protein-based therapeutic possibilities that will be discussed herein. Selective triggering of DR-mediated apoptosis in cancer cells is an emerging approach that is being intensely investigated as a mode of cancer therapy. Local administration of Fas agonists, and more promisingly, systemic use of soluble recombinant forms of TRAIL have shown efficacy in preclinical models of the disease. Developments in this field that may have important clinical implications for the treatment of cancer are reviewed.

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Authors: French, L. E., & Tschopp, J.
Affiliations: University of Geneva (CH)
University of Lausanne (CH)
Corresponding author: French, Lars E
ORCID: French, Lars E
Venue: Cell Death & Differentiation
Publisher: Springer Science and Business Media LLC
Published: 2003-01
Volume: 10
Issue: 1
Pages: 117-123
ISSN: 1350-9047 (ISSN-L)
1476-5403
DOI: 10.1038/sj.cdd.4401185
OpenAlex: W2035127186
Cited by: 102
References: 50
Citations by year: 2026: 1 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 6 · 2015: 9 · 2014: 4 · 2013: 3 · 2012: 6
FWCI: 0.78
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Cell Death and Differentiation (publishedVersion)
PubMed (publishedVersion)
IRIS (submittedVersion)
SERVAL (Université de Lausanne) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Immunology and Microbiology › Immunology › Toxin Mechanisms and Immunotoxins
Keywords: death receptors, Fas, Fas ligand, TRAIL, TRAIL-R1, DR5, apoptosis, cancer therapy, immune homeostasis, graft-versus-host disease, toxic epidermal necrolysis, multiple sclerosis, stroke, therapeutic proteins
MeSH terms: Animals, Antineoplastic Agents, Eukaryotic Cells, Humans, Membrane Glycoproteins, Neoplasms, Tumor Necrosis Factor-alpha, Apoptosis, fas Receptor, Apoptosis Regulatory Proteins, TNF-Related Apoptosis-Inducing Ligand, Fas Ligand Protein

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