000048664 001__ 48664 000048664 005__ 20200221144343.0 000048664 0247_ $$2doi$$a10.1038/cdd.2015.174 000048664 0248_ $$2sideral$$a94617 000048664 037__ $$aART-2016-94617 000048664 041__ $$aeng 000048664 100__ $$0(orcid)0000-0002-8486-8514$$aDe Miguel, D. 000048664 245__ $$aOnto better TRAILs for cancer treatment 000048664 260__ $$c2016 000048664 5060_ $$aAccess copy available to the general public$$fUnrestricted 000048664 5203_ $$aTumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), also known as Apo-2 ligand (Apo2L), is a member of the TNF cytokine superfamily. By cross-linking TRAIL-Receptor (TRAIL-R) 1 or TRAIL-R2, also known as death receptors 4 and 5 (DR4 and DR5), TRAIL has the capability to induce apoptosis in a wide variety of tumor cells while sparing vital normal cells. The discovery of this unique property among TNF superfamily members laid the foundation for testing the clinical potential of TRAIL-R-targeting therapies in the cancer clinic. To date, two of these therapeutic strategies have been tested clinically: (i) recombinant human TRAIL and (ii) antibodies directed against TRAIL-R1 or TRAIL-R2. Unfortunately, however, these TRAIL-R agonists have basically failed as most human tumors are resistant to apoptosis induction by them. It recently emerged that this is largely due to the poor agonistic activity of these agents. Consequently, novel TRAIL-R-targeting agents with increased bioactivity are currently being developed with the aim of rendering TRAIL-based therapies more active. This review summarizes these second-generation novel formulations of TRAIL and other TRAIL-R agonists, which exhibit enhanced cytotoxic capacity toward cancer cells, thereby providing the potential of being more effective when applied clinically than first-generation TRAIL-R agonists. 000048664 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/PI13-00416$$9info:eu-repo/grantAgreement/ES/MICINN/SAF2013-48626-C2-1-R 000048664 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-sa$$uhttp://creativecommons.org/licenses/by-nc-sa/3.0/es/ 000048664 590__ $$a8.339$$b2016 000048664 591__ $$aCELL BIOLOGY$$b25 / 189 = 0.132$$c2016$$dQ1$$eT1 000048664 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b24 / 287 = 0.084$$c2016$$dQ1$$eT1 000048664 592__ $$a4.319$$b2016 000048664 593__ $$aMolecular Biology$$c2016$$dQ1 000048664 593__ $$aCell Biology$$c2016$$dQ1 000048664 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000048664 700__ $$aLemke, J. 000048664 700__ $$0(orcid)0000-0002-5175-8394$$aAnel, A.$$uUniversidad de Zaragoza 000048664 700__ $$aWalczak, H. 000048664 700__ $$0(orcid)0000-0003-3043-147X$$aMartinez-Lostao, L.$$uUniversidad de Zaragoza 000048664 7102_ $$11008$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Inmunología 000048664 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole. 000048664 773__ $$g23, 5 (2016), 733-747$$pCell death differ.$$tCell Death and Differentiation$$x1350-9047 000048664 8564_ $$s1483671$$uhttps://zaguan.unizar.es/record/48664/files/texto_completo.pdf$$yVersión publicada 000048664 8564_ $$s117687$$uhttps://zaguan.unizar.es/record/48664/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000048664 909CO $$ooai:zaguan.unizar.es:48664$$particulos$$pdriver 000048664 951__ $$a2020-02-21-13:51:18 000048664 980__ $$aARTICLE