Apatinib resistance mediated by IRF9 nuclear translocation in head and neck squamous cell carcinoma

Yi Song1, Jie Lou2, Jin Xu3

  • 1Department of Stomatology, School of Medicine, Taizhou Polytechnic College, Taizhou 225300, China.

Iscience
|August 1, 2026
PubMed

Insights

Interferon regulatory factor 9 (IRF9) drives apatinib resistance in head and neck squamous cell carcinoma (HNSCC). Targeting IRF9 with HY-N1435 (Oroxin B) may overcome this resistance, offering new therapeutic strategies for HNSCC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Apatinib is a crucial treatment for head and neck squamous cell carcinoma (HNSCC).
  • Clinical resistance to apatinib is a significant challenge in HNSCC treatment.
  • The molecular mechanisms underlying apatinib resistance in HNSCC are not fully understood.

Purpose of the Study:

  • To identify key determinants of apatinib resistance in HNSCC.
  • To elucidate the mechanism by which apatinib resistance occurs.
  • To explore potential therapeutic strategies to overcome apatinib resistance.

Main Methods:

  • Establishment of apatinib-resistant HNSCC cell lines.
  • Small molecule protein interaction assay (SPIA) to identify drug resistance factors.
  • Investigation of IRF9's role in nuclear translocation and downstream signaling pathways.
  • Evaluation of HY-N1435 (Oroxin B) efficacy in reversing apatinib resistance.

Main Results:

  • Interferon regulatory factor 9 (IRF9) was identified as a critical determinant of apatinib resistance.
  • Apatinib enhances IRF9's nuclear translocation, promoting tumor progression via basal cell carcinoma and JAK-STAT pathways.
  • Higher IRF9 protein expression correlates with increased apatinib resistance.
  • HY-N1435 (Oroxin B) effectively reversed apatinib resistance in HNSCC models.

Conclusions:

  • IRF9 is a key mediator of apatinib resistance in HNSCC.
  • Targeting IRF9 presents a promising therapeutic strategy for overcoming apatinib resistance in HNSCC.
  • Understanding IRF9's role provides critical insights into HNSCC treatment resistance.

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