48664 20200221144343.0 doi 10.1038/cdd.2015.174 sideral 94617 ART-2016-94617 eng (orcid)0000-0002-8486-8514 De Miguel, D. Onto better TRAILs for cancer treatment 2016 Access copy available to the general public Unrestricted 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. info:eu-repo/grantAgreement/ES/ISCIII/PI13-00416 info:eu-repo/grantAgreement/ES/MICINN/SAF2013-48626-C2-1-R info:eu-repo/semantics/openAccess by-nc-sa http://creativecommons.org/licenses/by-nc-sa/3.0/es/ 8.339 2016 CELL BIOLOGY 25 / 189 = 0.132 2016 Q1 T1 BIOCHEMISTRY & MOLECULAR BIOLOGY 24 / 287 = 0.084 2016 Q1 T1 4.319 2016 Molecular Biology 2016 Q1 Cell Biology 2016 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Lemke, J. (orcid)0000-0002-5175-8394 Anel, A. Universidad de Zaragoza Walczak, H. (orcid)0000-0003-3043-147X Martinez-Lostao, L. Universidad de Zaragoza 1008 566 Universidad de Zaragoza Dpto. Microb.Med.Pr.,Sal.Públ. Área Inmunología 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 23, 5 (2016), 733-747 Cell death differ. Cell Death and Differentiation 1350-9047 1483671 http://zaguan.unizar.es/record/48664/files/texto_completo.pdf Versión publicada 117687 http://zaguan.unizar.es/record/48664/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:48664 articulos driver 2020-02-21-13:51:18 ARTICLE