Broad-spectrum Cross-resistance to Anticancer Drugs Mediated by Epidermal Growth Factor Receptor

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. This study systematically investigated the correlation of mRNA and protein expression of EGFR, as well as gene amplification and mut...

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Bibliographic Details
Published in:Anticancer research 2019-07, Vol.39 (7), p.3585-3593
Main Authors: Yan, G E, Efferth, Thomas
Format: Article
Language:English
Subjects:
Alkylating agents
Alkylation
Antibiotics
Anticancer properties
Antineoplastic Agents - pharmacology
Antineoplastic drugs
Antitumor agents
Cancer
Cell Line, Tumor
Correlation analysis
Cross-resistance
Cytotoxicity
Deoxyribonucleic acid
DNA
DNA topoisomerase
Drug resistance
Drug Resistance, Neoplasm - drug effects
Drug Resistance, Neoplasm - physiology
Drugs
Epidermal growth factor
Epidermal growth factor receptors
ErbB Receptors - physiology
Gene amplification
Gene expression
Growth factors
Hormones
Humans
Inhibitors
mRNA
Mutation
Natural products
Neoplasms - drug therapy
Neoplasms - genetics
Neoplasms - metabolism
Platinum
Protein expression
Proteins
RNA, Messenger - metabolism
Tumor cell lines
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Summary: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. 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 (log IC ) 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. EGFR protein expression, rather than other measurements, was most frequently associated with drug response. Log IC 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. 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.
ISSN:0250-7005
1791-7530
DOI:10.21873/anticanres.13505