Related Experiment Video
Updated: Jan 22, 2026
Studying the Stoichiometry of Epidermal Growth Factor Receptor in Intact Cells using Correlative Microscopy
Published on: September 11, 2015
Broad-spectrum Cross-resistance to Anticancer Drugs Mediated by Epidermal Growth Factor Receptor
1Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
Background:
The oncogenic role of epidermal growth factor receptor (EGFR) has been intensively studied. However, its emerging role in drug resistance has not been fully addressed.
Materials And Methods:
This study systematically investigated the correlation of mRNA and protein expression of EGFR, as well as gene amplification and mutations with the log-transformed half-maximal inhibitory concentration (log10IC50) values obtained from the NCI panel of 60 human tumor cell lines against 83 standard anticancer agents and the top 10 natural cytotoxic products previously screened by us.
Results:
EGFR protein expression, rather than other measurements, was most frequently associated with drug response. Log10IC50 and EGFR protein level were significantly positively correlated under all investigated DNA topoisomerase (TOPO) II inhibitors, followed by 81% of alkylating agents and platinum-based compounds, 71% of anti-hormones, 66% of TOPO I inhibitors and 50% of antibiotics. Furthermore, 60% of cytotoxic natural products did not reveal significant correlations.
Conclusion:
Collectively, we showed a broad-spectrum of cross-resistance towards clinical drugs mediated by EGFR. Natural cytotoxic products may be further developed as novel drugs to overcome EGFR-associated resistance to clinically established anticancer drugs.
Insights
Epidermal growth factor receptor (EGFR) protein levels strongly correlate with resistance to many anticancer drugs. Natural compounds show promise in overcoming this EGFR-mediated drug resistance.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Epidermal growth factor receptor (EGFR) is a known oncogene.
- The role of EGFR in anticancer drug resistance requires further investigation.
Purpose of the Study:
- To investigate the association between EGFR expression (mRNA, protein, gene amplification, mutations) and drug sensitivity.
- To explore EGFR's role in cross-resistance to various anticancer agents and natural products.
Main Methods:
- Utilized the NCI-60 human tumor cell line panel.
- Correlated EGFR expression levels with drug response (log10IC50) to 83 standard anticancer agents and 10 natural cytotoxic products.
Main Results:
- EGFR protein expression was the most frequent correlate of drug response.
- Significant positive correlations were observed between EGFR protein levels and resistance to DNA topoisomerase II inhibitors, alkylating agents, platinum compounds, anti-hormones, and topoisomerase I inhibitors.
- EGFR protein expression showed limited correlation with resistance to antibiotics and natural cytotoxic products.
Conclusions:
- EGFR mediates a broad spectrum of cross-resistance to clinical anticancer drugs.
- Natural cytotoxic products may serve as potential therapeutic agents to overcome EGFR-associated drug resistance.
More Related Videos
Related Concept Videos
01:39Receptor-mediated Endocytosis
01:20Receptor-mediated Endocytosis
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
01:18Factors Affecting Protein-Drug Binding: Drug-Related Factors
One crucial factor in drug-protein binding is the drug's lipophilicity or its affinity for fat. More lipophilic drugs tend to have higher binding extents. For example, highly lipophilic drugs like cloxacillin exhibit substantial protein binding, with as much as 95% of the drug binding to proteins. In...
01:19Factors Affecting Drug Distribution: Miscellaneous Factors
Age plays a significant role due to differences in body composition among different age groups. Infants, for instance, have a higher proportion of total body water and lower albumin levels, a protein that binds drugs in the bloodstream. This unique composition in infants enhances the...
01:28Role of Hematopoietic Growth Factors
Thrombopoietin (TPO), mainly released by the liver,...
01:29Factors Influencing Microbial Growth: pH