title: The JAK2/STAT5 signaling pathway as a potential therapeutic target in canine mastocytoma.
abstract: BACKGROUND
  Mastocytoma are frequently diagnosed cutaneous neoplasms in dogs. In non-resectable mastocytoma patients, novel targeted drugs are often applied. The transcription factor STAT5 has been implicated in the survival of human neoplastic mast cells (MC). Our study evaluated the JAK2/STAT5 pathway as a novel target in canine mastocytoma.
  
  
  METHODS
  We employed inhibitors of JAK2 (R763, TG101348, AZD1480, ruxolitinib) and STAT5 (pimozide, piceatannol) and evaluated their effects on 2 mastocytoma cell lines, C2 and NI-1.
  
  
  RESULTS
  Activated JAK2 and STAT5 were detected in both cell lines. The drugs applied were found to inhibit proliferation and survival in these cells with the following rank-order of potency: R763 > TG101348 > AZD1480 > pimozide > ruxolitinib > piceatannol. Moreover, synergistic anti-neoplastic effects were obtained by combining pimozide with KIT-targeting drugs (toceranib, masitinib, nilotinib, midostaurin) in NI-1 cells.
  
  
  CONCLUSIONS
  The JAK2/STAT5 pathway is a novel potential target of therapy in canine mastocytoma.
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.|Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
authors.forename: Alexandra
authors.identifier: http://orcid.org/0000-0001-8843-7001
authors.initials: A
authors.lastname: Keller
authors.affiliation: Ludwig Boltzmann Institute for Cancer Research, Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Medical University of Vienna, Vienna, Austria.
authors.forename: Bettina
authors.initials: B
authors.lastname: Wingelhofer
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.|Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Peter
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Bauer
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Berger
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Gamperl
authors.affiliation: Institute of Pathology and Forensic Veterinary Medicine, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Reifinger
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.|Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Cerny-Reiterer
authors.affiliation: Ludwig Boltzmann Institute for Cancer Research, Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Medical University of Vienna, Vienna, Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Moriggl
authors.affiliation: Department of Companion Animals and Horses, Small Animal Clinic, Internal Medicine, University of Veterinary Medicine Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Willmann
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.|Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.|Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.|Department of Companion Animals and Horses, Small Animal Clinic, Internal Medicine, University of Veterinary Medicine Vienna, Vienna, Austria.
authors.forename: Emir
authors.initials: E
authors.lastname: Hadzijusufovic
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004283:Dog Diseases / Q000188:drug therapy / Q000378:metabolism*; D004285:Dogs; D005434:Flow Cytometry / Q000662:veterinary; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034801:Mastocytoma / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D009570:Nitriles; D009636:Norbornanes / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D050799:STAT5 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D053614:Janus Kinase 2; D009570:Nitriles; D009636:Norbornanes; D010868:Pimozide; D011720:Pyrazoles; D011743:Pyrimidines; D011759:Pyrrolidines; D050799:STAT5 Transcription Factor; D013267:Stilbenes; D013449:Sulfonamides; C545606:AZD 1480; C000592140:MSC1992371A; C041525:3,3',4,5'-tetrahydroxystilbene; C528327:fedratinib; D000096926:Benzenesulfonamides; C540383:ruxolitinib
keywords: 
  JAK2
  ; 
  KIT
  ; 
  STAT5
  ; canine mastocytoma; targeted drugs