Drug combination approach to overcome resistance to EGFR tyrosine kinase inhibitors in lung cancer
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AbstractThe discovery of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) has led to unprecedented clinical response in a subset of lung cancer patients carrying the sensitizing EGFR mutations (L858R or exon 19 deletion). However, disease progression invariably occurs within a year after the initial TKI treatment, predominantly due to the development of acquired resistance caused by the secondary EGFR T790 M mutation. Numerous second generation irreversible and third generation EGFR T790 M selective EGFR TKIs have been developed to overcome resistance. Besides developing new EGFR TKIs, combination therapy represents another promising strategy to combat resistance. This approach aims at circumventing drug resistance through a so-called bypass signaling mechanism by targeting horizontal pathways or vertical pathways or both. The logical combinations of different molecular targeted drugs inhibiting various oncogenic signaling have been studied. On the other hand, the repurposing of drugs with indications other than oncology has also emerged as a promising approach. In this review, we focus on the effectiveness of combination therapy of EGFR-TKIs with different agents in advanced lung cancer.
All Author(s) ListTong CWS, Wu WKK, Loong HHF, Cho WCS, To KKW
Journal nameCancer Letters
Year2017
Month10
Day1
Volume Number405
PublisherElsevier
Pages100 - 110
ISSN0304-3835
eISSN1872-7980
LanguagesEnglish-United States
KeywordsEpidermal growth factor receptor tyrosine kinase inhibitor, Drug resistance, Drug combination, Lung cancer, Signaling bypass, Drug repurposing

Last updated on 2021-19-02 at 01:10