Cancer-selective targeting of the NF-kappaB survival pathway with GADD45beta/MKK7 inhibitors(763 views) Tornatore L, Sandomenico A, Raimondo D, Low C, Rocci A, Tralau-Stewart C, Capece D, D'Andrea D, Bua M, Boyle E, van Duin M, Zoppoli P, Jaxa-Chamiec A, Thotakura AK, Dyson J, Walker BA, Leonardi A, Chambery A, Driessen C, Sonneveld P, Morgan G, Palumbo A, Tramontano A, Rahemtulla A, Ruvo M, Franzoso G
Cancer Cell (ISSN: 1535-6108), 2014 Oct 13; 26(4): 495-508.
Keywords: Antineoplastic Agent, Bortezomib, D Tripeptide Dtp3, Growth Arrest And Dna Damage Inducible Protein 45 Beta Inhibitor, Immunoglobulin Enhancer Binding Protein, Jnk Kinase Mkk7, Jnk Kinase Mkk7 Inhibitor, Protein Inhibitor, Stress Activated Protein Kinase Inhibitor, Tripeptide Derivative, Unclassified Drug, Cell Cycle Protein, Gadd45a Protein, Human, Map2k7 Protein, Mitogen Activated Protein Kinase Kinase 7, Nuclear Protein, Animal Experiment, Animal Model, Antineoplastic Activity, Cancer Cell, Controlled Study, Human Cell, In Vitro Study, Mouse, Multiple Myeloma, Nonhuman, Protein Expression, Protein Protein Interaction, Signal Transduction, Survival Factor, Tumor Xenograft, Antagonists And Inhibitors, Bioavailability, Metabolism, Pathology, Biological Availability, Map Kinase Kinase 7, Nf-Kappa B, Antineoplastic Agents Pharmacokinetics Pharmacology, Cell Cycle Proteins Antagonists, Map Kinase Kinase 7 Antagonists, Multiple Myeloma Metabolism Pathology, Nf-Kappa B Metabolism, Nuclear Proteins Antagonists,
Affiliations: *** IBB - CNR ***
Department of Medicine, Centre for Cell Signalling and Inflammation, Imperial College LondonLondon, United Kingdom
Institute of Biostructures and Bioimages, National Research Council and CIRPeBNaples, Italy
Department of Physics, Sapienza UniversityRome, Italy
Drug Discovery Centre, Imperial College LondonLondon, United Kingdom
Division of Hematology, University of Torino, AOU San Giovanni BattistaTurin, Italy
Section of Haemato-Oncology, The Institute of Cancer ResearchLondon, United Kingdom
Department of Hematology, Erasmus University Medical CenterCA Rotterdam, Netherlands
Institute for Cancer Genetics, Columbia University Medical CenterNew York, NY, United States
Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico IINaples, Italy
Department of Environmental, Biological, and Pharmaceutical Sciences and Technologies, Second University of NaplesCaserta, Italy
IRCCS MultimedicaMilan, Italy
Department of Oncology/Hematology, Kantonsspital St. GallenSt. Gallen, Switzerland
Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza UniversityRome, Italy
IRCCS Multimedica, 20138 Milan, Italy.
References: Not available.
Cancer-selective targeting of the NF-kappaB survival pathway with GADD45beta/MKK7 inhibitors
Constitutive NF-kappaB signaling promotes survival in multiple myeloma (MM) and other cancers; however, current NF-kappaB-targeting strategies lack cancer cell specificity. Here, we identify the interaction between the NF-kappaB-regulated antiapoptotic factor GADD45beta and the JNK kinase MKK7 as a therapeutic target in MM. Using a drug-discovery strategy, we developed DTP3, a D-tripeptide, which disrupts the GADD45beta/MKK7 complex, kills MM cells effectively, and, importantly, lacks toxicity to normal cells. DTP3 has similar anticancer potency to the clinical standard, bortezomib, but more than 100-fold higher cancer cell specificity in vitro. Notably, DTP3 ablates myeloma xenografts in mice with no apparent side effects at the effective doses. Hence, cancer-selective targeting of the NF-kappaB pathway is possible and, at least for myeloma patients, promises a profound benefit.
Cancer-selective targeting of the NF-kappaB survival pathway with GADD45beta/MKK7 inhibitors
No results.
Cancer-selective targeting of the NF-kappaB survival pathway with GADD45beta/MKK7 inhibitors
Petraglia F, Singh AA, Carafa V, Nebbioso A, Conte M, Scisciola L, Valente S, Baldi A, Mandoli A, Petrizzi VB, Ingenito C, De Falco S, Cicatiello V, Apicella I, Janssen-megens EM, Kim B, Yi G, Logie C, Heath S, Ruvo M, Wierenga ATJ, Flicek P, Yaspo ML, Della Valle V, Bernard O, Tomassi S, Novellino E, Feoli A, Sbardella G, Gut I, Vellenga E, Stunnenberg HG, Mai A, Martens JHA, Altucci L * Combined HAT/EZH2 modulation leads to cancer-selective cell death(455 views) Oncotarget (ISSN: 1949-2553electronic, 1949-2553linking), 2018 May 22; 9(39): 25630-25646. Impact Factor:5.008 ViewExport to BibTeXExport to EndNote
Vitiello M, Finamore E, Falanga A, Raieta K, Cantisani M, Galdiero F, Pedone C, Galdiero M, Galdiero S * Fusion in Coq(600 views) Lecture Notes In Computer Science (ISSN: 0302-9743, 0302-974335404636319783540463634, 0302-974335402975459783540297543), 2001; 2178LNCS: 583-596. Impact Factor:0.415 ViewExport to BibTeXExport to EndNote