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<p>Janus kinase (JAK) is a tyrosine kinase that binds to cytokine receptors and regulates transcription through signal transducer and activator of transcription (STAT) phosphorylation. Oclacitinib is a JAK1 inhibitor that is approved for the treatment of canine atopic dermatitis because it inhibits IL-31 signaling. Recent studies suggest clinical remission in dogs with cutaneous lymphoma treated with oclacitinib; however, the underlying mechanisms remain unclear. Its effects on high-grade canine lymphomas beyond cutaneous lymphoma are unknown. In this study, we examined the antitumor mechanism of oclacitinib in canine cutaneous lymphoma and determined its effects on high-grade canine lymphoma cell lines in vitro. EO-1 (cutaneous lymphoma) and eight high-grade lymphoma cell lines were treated with oclacitinib. Growth inhibition, cell death, G0/G1 phase cell cycle arrest, and apoptosis based on caspase-3 activation were observed in five sensitive cell lines. JAK1 and STAT5 phosphorylation was detected in these cells and decreased upon treatment, suggesting a dependence on JAK1/STAT5 signaling. In canine cutaneous lymphoma tissues, JAK1/STAT5 phosphorylation correlated with clinical sensitivity to oclacitinib. Similar phosphorylation profiles were observed in some multicentric and gastrointestinal lymphomas, suggesting broader applicability. Taken together, the results indicate that oclacitinib exerts antitumor effects by inhibiting JAK1/STAT5 signaling. The phosphorylation of these proteins may serve as a biomarker for predicting response to this inhibitor in canine lymphoma.</p>

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The antitumor mechanism of oclacitinib in canine lymphoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月12日

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  • Miruki Harada,
  • Sakuya Inanaga,
  • Masashi Sakurai,
  • Shusaku Shibutani,
  • Takehito Sugasawa,
  • Nobuo Murayama,
  • Takafumi Osumi,
  • Yuta Baba,
  • Hiroki Sakai,
  • Sadatoshi Maeda,
  • Masaya Igase,
  • Takuya Mizuno

摘要

Janus kinase (JAK) is a tyrosine kinase that binds to cytokine receptors and regulates transcription through signal transducer and activator of transcription (STAT) phosphorylation. Oclacitinib is a JAK1 inhibitor that is approved for the treatment of canine atopic dermatitis because it inhibits IL-31 signaling. Recent studies suggest clinical remission in dogs with cutaneous lymphoma treated with oclacitinib; however, the underlying mechanisms remain unclear. Its effects on high-grade canine lymphomas beyond cutaneous lymphoma are unknown. In this study, we examined the antitumor mechanism of oclacitinib in canine cutaneous lymphoma and determined its effects on high-grade canine lymphoma cell lines in vitro. EO-1 (cutaneous lymphoma) and eight high-grade lymphoma cell lines were treated with oclacitinib. Growth inhibition, cell death, G0/G1 phase cell cycle arrest, and apoptosis based on caspase-3 activation were observed in five sensitive cell lines. JAK1 and STAT5 phosphorylation was detected in these cells and decreased upon treatment, suggesting a dependence on JAK1/STAT5 signaling. In canine cutaneous lymphoma tissues, JAK1/STAT5 phosphorylation correlated with clinical sensitivity to oclacitinib. Similar phosphorylation profiles were observed in some multicentric and gastrointestinal lymphomas, suggesting broader applicability. Taken together, the results indicate that oclacitinib exerts antitumor effects by inhibiting JAK1/STAT5 signaling. The phosphorylation of these proteins may serve as a biomarker for predicting response to this inhibitor in canine lymphoma.