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Updated: Apr 15, 2026

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JAK kinase inhibition abrogates STAT3 activation and head and neck squamous cell carcinoma tumor growth

Malabika Sen1, Netanya I Pollock1, John Black1

  • 1Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Neoplasia (New York, N.Y.)
|March 27, 2015
PubMed

Insights

AZD1480, a Janus kinase (JAK) inhibitor, effectively reduced head and neck squamous cell carcinoma (HNSCC) growth in preclinical models by inhibiting STAT3 signaling. This suggests JAK inhibitors may be a viable HNSCC therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Aberrant Janus kinase (JAK)/signal transducer and activator of transcription (STAT) 3 signaling is crucial for head and neck squamous cell carcinoma (HNSCC) proliferation and survival.
  • AZD1480 is an orally available inhibitor targeting JAK1/JAK2, previously explored in various cancer models.

Purpose of the Study:

  • To evaluate the in vitro and in vivo efficacy of AZD1480 in preclinical models of HNSCC.
  • To determine the potential of JAK kinase inhibition as a therapeutic approach for HNSCC.

Main Methods:

  • In vitro assessment of AZD1480's effect on HNSCC cell line proliferation and pSTAT3(Tyr705) expression.
  • In vivo evaluation of AZD1480's antitumor efficacy using patient-derived xenograft (PDX) models of HNSCC.

Main Results:

  • AZD1480 significantly decreased HNSCC cell proliferation in vitro, with EC50 values between 0.9–4 μM, accompanied by reduced pSTAT3(Tyr705) levels.
  • Oral administration of AZD1480 demonstrated antitumor efficacy in two independent HNSCC PDX models, reducing tumor growth.
  • Decreased pSTAT3(Tyr705) expression was confirmed in tumors from both in vivo models following AZD1480 treatment.

Conclusions:

  • AZD1480 effectively inhibits JAK1/2, leading to the abrogation of STAT3 signaling in HNSCC.
  • These findings support the potential of JAK1/2 inhibitors like AZD1480 as a therapeutic strategy for HNSCC.

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