Related Experiment Video
Updated: Oct 27, 2025
Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
IGFBP7 overexpression promotes acquired resistance to AZD9291 in non-small cell lung cancer
Xiaonan Tang1, Jing Mu2, Li Ma1
1Department of Medical Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute/Beijing Chest Hospital, Capital Medical University, Beijing, 101149, China.
Abstract:
AZD9291 (osimertinib) is the third-generation EGFR-TKI treat for EGFR mutated NSCLC patients. Despite its encouraging efficacy in clinical, acquired resistance is still inevitable. The mechanism of drug resistance needs to be further explored. In a previous study, we established an AZD9291-resistant cell strain named HCC827/AZDR. We found that insulin-like growth factor binding protein 7 (IGFBP7) expression was markedly increased in HCC827/AZDR cells and AZD9291-resistant patients by RNA sequencing and immunohistochemical analysis, respectively. Reduced IGFBP7 in HCC827/AZDR cells by si-RNA interference recovered the sensitivity to AZD9291 partially and increased AZD9291-induced cell apoptosis. Enhancing IGFBP7 expression in EGFR-mutated non-small cell lung cancer (NSCLC) cells using lentiviruses infection reduced their sensitivity to AZD9291. This study is the first to discover that high IGFBP7 expression could occur following treatment with AZD9291. This might be one of the mechanisms underlying AZD9291 resistance and a potential therapeutic target following AZD9291 resistance.
Insights
Insulin-like growth factor binding protein 7 (IGFBP7) upregulation is a newly discovered mechanism of resistance to AZD9291 (osimertinib) in EGFR-mutated non-small cell lung cancer (NSCLC). Targeting IGFBP7 may overcome this acquired resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) like AZD9291 (osimertinib) are effective for EGFR-mutated non-small cell lung cancer (NSCLC).
- Acquired resistance to AZD9291 is a significant clinical challenge, necessitating exploration of underlying mechanisms.
- Understanding resistance mechanisms is crucial for developing strategies to improve patient outcomes.
Purpose of the Study:
- To investigate the role of insulin-like growth factor binding protein 7 (IGFBP7) in acquired resistance to AZD9291 in EGFR-mutated NSCLC.
- To determine if IGFBP7 expression is altered in AZD9291-resistant cells and patients.
- To evaluate IGFBP7 as a potential therapeutic target for overcoming AZD9291 resistance.
Main Methods:
- Establishment of an AZD9291-resistant NSCLC cell line (HCC827/AZDR).
- RNA sequencing and immunohistochemical analysis to assess IGFBP7 expression.
- si-RNA interference to reduce IGFBP7 levels in resistant cells.
- Lentiviral vectors to enhance IGFBP7 expression in sensitive cells.
Main Results:
- IGFBP7 expression was significantly increased in AZD9291-resistant HCC827/AZDR cells and in AZD9291-resistant patient samples.
- Reducing IGFBP7 levels partially restored sensitivity to AZD9291 and enhanced apoptosis in resistant cells.
- Increasing IGFBP7 expression in sensitive EGFR-mutated NSCLC cells reduced their responsiveness to AZD9291.
Conclusions:
- This study identifies high IGFBP7 expression as a novel mechanism contributing to AZD9291 resistance in EGFR-mutated NSCLC.
- IGFBP7 may serve as a predictive biomarker for AZD9291 treatment response.
- Targeting IGFBP7 presents a potential therapeutic strategy to overcome acquired AZD9291 resistance in NSCLC patients.
More Related Videos
09:38Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
13:34A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds
Published on: April 6, 2016
