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The JAK2/STAT5 signaling pathway as a potential therapeutic target in canine mastocytoma

Alexandra Keller1,2, Bettina Wingelhofer3, Barbara Peter1,2

  • 1Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.

Veterinary and Comparative Oncology
|April 12, 2017
PubMed
Abstract

Insights

Targeting the JAK2/STAT5 pathway shows promise for treating canine mastocytoma. Inhibiting this pathway with novel drugs effectively reduced cancer cell proliferation and survival in preclinical models.

Area of Science:

  • Veterinary Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Mastocytoma is a common skin cancer in dogs, often requiring targeted therapies for non-resectable cases.
  • The Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) pathway is crucial for neoplastic mast cell survival in humans.
  • This study investigates the JAK2/STAT5 pathway as a potential therapeutic target in canine mastocytoma.

Purpose of the Study:

  • To evaluate the JAK2/STAT5 signaling pathway as a novel therapeutic target in canine mastocytoma.
  • To assess the efficacy of JAK2 and STAT5 inhibitors in canine mastocytoma cell lines.

Main Methods:

  • Utilized two canine mastocytoma cell lines (C2 and NI-1).
  • Employed a panel of JAK2 inhibitors (R763, TG101348, AZD1480, ruxolitinib) and STAT5 inhibitors (pimozide, piceatannol).
  • Assessed the impact of these inhibitors on cell proliferation and survival.

Main Results:

  • Activated JAK2 and STAT5 were confirmed in both canine mastocytoma cell lines.
  • JAK2 and STAT5 inhibitors demonstrated significant inhibition of proliferation and survival.
  • A specific rank order of drug potency was established: R763 > TG101348 > AZD1480 > pimozide > ruxolitinib > piceatannol.
  • Synergistic anti-neoplastic effects were observed when combining a STAT5 inhibitor (pimozide) with KIT-targeting drugs in NI-1 cells.

Conclusions:

  • The JAK2/STAT5 pathway represents a promising novel therapeutic target for canine mastocytoma.
  • Targeting this pathway offers a potential new strategy for treating canine mastocytoma, particularly in challenging cases.
Keywords:
JAK2KITSTAT5canine mastocytomatargeted drugs

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