Related Experiment Video
Updated: Aug 5, 2026

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
Apatinib resistance mediated by IRF9 nuclear translocation in head and neck squamous cell carcinoma
1Department of Stomatology, School of Medicine, Taizhou Polytechnic College, Taizhou 225300, China.
Abstract:
Apatinib is being increasingly utilized in the treatment of head and neck squamous cell carcinoma (HNSCC) patients. However, clinical resistance to apatinib is commonly observed, the underlying mechanism remains unclear. In this study, we established apatinib-resistant HNSCC cell lines and performed SPIA (small molecule protein interaction assay) to identify interferon regulatory factor 9 (IRF9) as a critical determinant of drug resistance. Mechanistically, apatinib binds to IRF9, enhancing protein flexibility and ability to bind the nuclear transport protein RAN and translocate into the nucleus. Once translocated, IRF9 facilitates tumor progression by the basal cell carcinoma pathway and the JAK-STAT signaling pathway. HY-N1435 (Oroxin B), a small-molecule drug targeting IRF9, was found to reverse apatinib resistance in HNSCC. Moreover, higher IRF9 protein expression levels are associated with an increased likelihood of apatinib resistance. Taken together, the current study provided critical insights into the apatinib resistance mechanisms of HNSCC and proposed therapeutic strategies.
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.
More Related Videos
06:08Establishment and Characterization of Patient-Derived Xenograft Models of Anaplastic Thyroid Carcinoma and Head and Neck Squamous Cell Carcinoma
Published on: June 2, 2023
07:29Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Related Concept Videos
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Treatment Resistant Cancers
Targeted Cancer Therapies
There are several types of targeted therapies against specific...