title: Targeting melanoma with NT157 by blocking Stat3 and IGF1R signaling.
abstract: It is well known that specific signal transduction inhibitors rarely suffice as anti-cancer agents. In most cases, tumors possess primary drug resistance due to their inherent heterogeneity, or acquire drug resistance due to genomic instability and acquisition of mutations. Here we expand our previous study of the novel compound, NT157, and show that it acts as a dual-targeting agent that invokes the blockage of two signal transduction pathways that are central to the development and maintenance of multiple human cancers. We show that NT157 targets not only IGF1R-IRS1/2, as previously reported, but also the Stat3 signaling pathway and demonstrates remarkable anti-cancer characteristics in A375 human melanoma cells and in a metastatic melanoma model in mice.
authors.affiliation: Department of Biological Chemistry, Unit of Cellular Signaling, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Flashner-Abramson
authors.affiliation: Department of Biological Chemistry, Unit of Cellular Signaling, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Klein
authors.affiliation: Department of Biological Chemistry, Unit of Cellular Signaling, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Mullin
authors.affiliation: Department of Cancer Biology, Unit 173 UT, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: E
authors.initials: E
authors.lastname: Shoshan
authors.affiliation: Department of Cancer Biology, Unit 173 UT, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: R
authors.initials: R
authors.lastname: Song
authors.affiliation: Department of Biological Chemistry, Unit of Cellular Signaling, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Shir
authors.affiliation: Department of Biological Chemistry, Unit of Cellular Signaling, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Langut
authors.affiliation: Department of Cancer Biology, Unit 173 UT, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: M
authors.initials: M
authors.lastname: Bar-Eli
authors.affiliation: Department of Biological Chemistry, Unit of Cellular Signaling, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.|NovoTyr Ltd., Tel Hai, Israel.
authors.forename: H
authors.initials: H
authors.lastname: Reuveni
authors.affiliation: Department of Biological Chemistry, Unit of Cellular Signaling, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Levitzki
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D055808:Drug Discovery; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D058990:Molecular Targeted Therapy / Q000379:methods*; D009361:Neoplasm Invasiveness; D011748:Pyrogallol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; C000597236:IGF1R protein, human; C000622270:NT157 compound; D017451:Receptors, Somatomedin; D050796:STAT3 Transcription Factor; D013449:Sulfonamides; D011748:Pyrogallol; D017526:Receptor, IGF Type 1