Onto better TRAILs for cancer treatment

De Miguel, D. ; Lemke, J. ; Anel, A. (Universidad de Zaragoza) ; Walczak, H. ; Martinez-Lostao, L. (Universidad de Zaragoza)
Onto better TRAILs for cancer treatment
Resumen: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), also known as Apo-2 ligand (Apo2L), is a member of the TNF cytokine superfamily. By cross-linking TRAIL-Receptor (TRAIL-R) 1 or TRAIL-R2, also known as death receptors 4 and 5 (DR4 and DR5), TRAIL has the capability to induce apoptosis in a wide variety of tumor cells while sparing vital normal cells. The discovery of this unique property among TNF superfamily members laid the foundation for testing the clinical potential of TRAIL-R-targeting therapies in the cancer clinic. To date, two of these therapeutic strategies have been tested clinically: (i) recombinant human TRAIL and (ii) antibodies directed against TRAIL-R1 or TRAIL-R2. Unfortunately, however, these TRAIL-R agonists have basically failed as most human tumors are resistant to apoptosis induction by them. It recently emerged that this is largely due to the poor agonistic activity of these agents. Consequently, novel TRAIL-R-targeting agents with increased bioactivity are currently being developed with the aim of rendering TRAIL-based therapies more active. This review summarizes these second-generation novel formulations of TRAIL and other TRAIL-R agonists, which exhibit enhanced cytotoxic capacity toward cancer cells, thereby providing the potential of being more effective when applied clinically than first-generation TRAIL-R agonists.
Idioma: Inglés
DOI: 10.1038/cdd.2015.174
Año: 2016
Publicado en: Cell Death and Differentiation 23, 5 (2016), 733-747
ISSN: 1350-9047

Factor impacto JCR: 8.339 (2016)
Categ. JCR: CELL BIOLOGY rank: 25 / 189 = 0.132 (2016) - Q1 - T1
Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 24 / 287 = 0.084 (2016) - Q1 - T1

Factor impacto SCIMAGO: 4.319 - Molecular Biology (Q1) - Cell Biology (Q1)

Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI13-00416
Financiación: info:eu-repo/grantAgreement/ES/MICINN/SAF2013-48626-C2-1-R
Tipo y forma: Article (Published version)
Área (Departamento): Área Inmunología (Dpto. Microb.Med.Pr.,Sal.Públ.)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)

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 Record created 2016-05-10, last modified 2020-02-21

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