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Updated: Jun 4, 2025

Establishing 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
CKAP4 is a potential therapeutic target to overcome resistance to EGFR-TKIs in lung adenocarcinoma
Seongeun Song1, Sangmyung Rhee2
1Department of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea.
Background:
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard treatments for non-small cell lung cancer (NSCLC) patients with EGFR mutations; however, drug resistance limits their efficacy. Cytoskeleton-associated protein 4 (CKAP4) has been linked to cancer progression, but its role in EGFR-TKI resistance remains unclear.
Objective:
This study investigates the clinical relevance of CKAP4 as a therapeutic target to overcome EGFR-TKI resistance in lung adenocarcinoma (LUAD) patients.
Methods:
GEO datasets were analyzed to identify 24 differentially expressed genes associated with EGFR-TKI resistance, with CKAP4 selected via functional annotation and scoring using the VarElect tool. The prognostic significance of CKAP4 was evaluated using public databases, and its upregulation was confirmed in osimertinib-tolerant H1975 cells through quantitative reverse transcription-polymerase chain reaction.
Results:
Integrated bioinformatics analysis identified CKAP4 as strongly associated with EGFR-TKI resistance. Elevated CKAP4 expression was particularly linked to poorer clinical outcomes in LUAD patients. Notably, osimertinib-tolerant cells exhibited high CKAP4 expression, correlating positively with increased half-maximal inhibitory concentrations of EGFR-TKIs. LUAD patients with upregulated CKAP4 showed significantly reduced overall and relapse-free survival.
Conclusion:
This study underscores the prognostic value of CKAP4 in EGFR-mutated LUAD and highlights its potential as a therapeutic target to counter EGFR-TKI resistance.
Insights
Cytoskeleton-associated protein 4 (CKAP4) is a potential biomarker for overcoming resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer. High CKAP4 expression correlates with poor outcomes and reduced drug efficacy in lung adenocarcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard treatments for EGFR-mutated non-small cell lung cancer (NSCLC).
- Acquired drug resistance to EGFR-TKIs limits treatment efficacy in NSCLC patients.
- The role of Cytoskeleton-associated protein 4 (CKAP4) in EGFR-TKI resistance is not well understood.
Purpose of the Study:
- To investigate the clinical significance of CKAP4 as a therapeutic target for overcoming EGFR-TKI resistance.
- To evaluate the prognostic value of CKAP4 in lung adenocarcinoma (LUAD) patients treated with EGFR-TKIs.
Main Methods:
- Bioinformatic analysis of GEO datasets to identify genes associated with EGFR-TKI resistance.
- Functional annotation and scoring of candidate genes using the VarElect tool.
- Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to confirm CKAP4 upregulation in resistant cells.
Main Results:
- CKAP4 was identified as a gene strongly associated with EGFR-TKI resistance.
- Elevated CKAP4 expression correlated with poorer clinical outcomes and reduced survival in LUAD patients.
- Osimertinib-tolerant cells showed high CKAP4 expression, linked to increased EGFR-TKI resistance.
Conclusions:
- CKAP4 serves as a prognostic biomarker in EGFR-mutated LUAD.
- CKAP4 represents a potential therapeutic target to overcome EGFR-TKI resistance in LUAD.
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