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The antitumor mechanism of oclacitinib in canine lymphoma

Miruki Harada1, Sakuya Inanaga1, Masashi Sakurai2,3

  • 1Laboratory of Molecular Diagnostics and Therapeutics, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, 753-8515, Japan.

Scientific Reports
|February 12, 2026
PubMed

Insights

Oclacitinib, a Janus kinase (JAK) inhibitor, shows antitumor effects in canine lymphoma by blocking JAK1/STAT5 signaling. This mechanism may predict treatment response in dogs with various lymphoma types.

Area of Science:

  • Veterinary Oncology
  • Immunology
  • Molecular Biology

Background:

  • Oclacitinib is a JAK1 inhibitor approved for canine atopic dermatitis.
  • Its efficacy and mechanism in canine lymphoma, particularly high-grade types, are not fully understood.
  • Previous studies suggest potential benefits in canine cutaneous lymphoma.

Purpose of the Study:

  • To investigate the antitumor mechanisms of oclacitinib in canine cutaneous lymphoma.
  • To evaluate the effects of oclacitinib on high-grade canine lymphoma cell lines in vitro.
  • To determine if JAK1/STAT5 signaling is a key pathway and potential biomarker for oclacitinib response.

Main Methods:

  • Treatment of canine cutaneous lymphoma (EO-1) and eight high-grade lymphoma cell lines with oclacitinib.
  • Assessment of cell growth inhibition, cell death, cell cycle arrest (G0/G1), and apoptosis (caspase-3 activation).
  • Analysis of Janus kinase 1 (JAK1) and signal transducer and activator of transcription 5 (STAT5) phosphorylation levels before and after treatment, and correlation with clinical data.

Main Results:

  • Oclacitinib induced growth inhibition, cell death, G0/G1 cell cycle arrest, and apoptosis in five sensitive cell lines.
  • Sensitive cell lines exhibited JAK1 and STAT5 phosphorylation, which decreased after oclacitinib treatment, indicating pathway dependence.
  • JAK1/STAT5 phosphorylation in canine cutaneous lymphoma tissues correlated with clinical sensitivity, and similar profiles were seen in multicentric and gastrointestinal lymphomas.

Conclusions:

  • Oclacitinib exerts antitumor effects in canine lymphoma by inhibiting JAK1/STAT5 signaling.
  • JAK1/STAT5 phosphorylation can serve as a predictive biomarker for oclacitinib response in canine lymphoma.
  • The findings suggest broader applicability of oclacitinib beyond cutaneous lymphoma.

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