STAT3 Activation as a Predictive Biomarker for Ruxolitinib Response in Head and Neck Cancer.

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Increased Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3) pathway activity is implicated in head and neck squamous cell carcinoma (HNSCC) progression.
• JAKs are potential therapeutic targets for HNSCC treatment.

Purpose of the Study:

• To investigate the anticancer effects of ruxolitinib, a JAK1/2 inhibitor, in HNSCC preclinical models.
• To evaluate ruxolitinib's impact on STAT3 activation and tumor growth in HNSCC.

Main Methods:

• Assessed ruxolitinib's effects on HNSCC cell lines, including STAT3 activation, growth, and colony formation.
• Utilized patient-derived xenografts (PDXs) from HNSCC patients treated with neoadjuvant ruxolitinib to assess in vivo efficacy and STAT3 inhibition.

Main Results:

• Ruxolitinib inhibited STAT3 activation, cellular growth, and colony formation in HNSCC cell lines.
• Ruxolitinib significantly inhibited tumor growth in HNSCC xenograft models.
• Responses in PDXs correlated with clinical outcomes, with lower baseline STAT3 activation in responsive tumors.

Conclusions:

• Ruxolitinib shows significant antitumor activity in preclinical HNSCC models.
• Baseline STAT3 activation levels (pSTAT3 or total STAT3) could serve as predictive biomarkers for ruxolitinib response in HNSCC patients.