title: Resistance to TRAIL and how to surmount it.
abstract: Development of resistance to TRAIL-induced toxicity is one of the strategies used from tumor cells to escape destruction from the immune system. This process may occur through aberrant expression of functional receptors, overexpression of decoy receptors on tumor cell membrane, or malfunctioning of downstream signals triggered by specific ligation of TRAIL. Numerous cytostatic, but also noncytostatic, drugs like protease inhibitors and NO-hybridized molecules have been shown to revert sensitivity of neoplastic cells to TRAIL by means of different mechanisms. This paper will review the possible routes of reconstitution of sensitivity to TRAIL-mediated immune response by specific modulation of different signals responsible for the development of resistance at both the membrane and the intracellular levels. Moreover, we will review and suggest novel strategies, aimed at resetting immune cell efficiency in cancer treatment.
authors.affiliation: Department of Immunology, Institute for Biological Research Sinisa Stankovic, Belgrade University, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia.
authors.forename: Danijela
authors.initials: D
authors.lastname: Maksimovic-Ivanic
authors.forename: Stanislava
authors.initials: S
authors.lastname: Stosic-Grujicic
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.forename: Sanja
authors.initials: S
authors.lastname: Mijatovic
mesh_terms: D000818:Animals; D017209:Apoptosis; D006801:Humans; D009369:Neoplasms / Q000276:immunology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000276:immunology* / Q000378:metabolism; D019258:Saquinavir / Q000494:pharmacology; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000276:immunology* / Q000378:metabolism; D019139:Tumor Escape
chemical_list: D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D019258:Saquinavir