Title |
Update on recent preclinical and clinical studies of T790M mutant-specific irreversible epidermal growth factor receptor tyrosine kinase inhibitors
|
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Published in |
Journal of Biomedical Science, December 2016
|
DOI | 10.1186/s12929-016-0305-9 |
Pubmed ID | |
Authors |
Bin-Chi Liao, Chia-Chi Lin, Jih-Hsiang Lee, James Chih-Hsin Yang |
Abstract |
The first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (1/2G EGFR-TKIs) gefitinib, erlotinib, and afatinib have all been approved as standard first-line treatments for advanced EGFR mutation-positive non-small cell lung cancer. The third-generation (3G) EGFR-TKIs have been developed to overcome the EGFR T790M mutation, which is the most common mechanism of acquired resistance to 1/2G EGFR-TKI treatment. This resistance mutation develops in half of the patients who respond to 1/2G EGFR-TKI therapy. The structures of the novel 3G EGFR-TKIs are different from those of 1/2G EGFR-TKIs. Particularly, 3G EGFR-TKIs have lower affinity to wild-type EGFR, and are therefore associated with lower rates of skin and gastrointestinal toxicities. However, many of the adverse events (AEs) that are observed in patients receiving 3G EGFR-TKIs have not been observed in patients receiving 1/2G EGFR-TKIs. Although preclinical studies have revealed many possible mechanisms for these AEs, the causes of some AEs remain unknown. Many mechanisms of resistance to 3G EGFR-TKI therapy have also been reported. Here, we have reviewed the recent clinical and preclinical developments related to novel 3G EGFR-TKIs, including osimertinib, rociletinib, olmutinib, EGF816, and ASP8273. |
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Geographical breakdown
Country | Count | As % |
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Unknown | 65 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Bachelor | 6 | 9% |
Other | 5 | 8% |
Student > Ph. D. Student | 5 | 8% |
Researcher | 5 | 8% |
Student > Master | 5 | 8% |
Other | 14 | 22% |
Unknown | 25 | 38% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 14 | 22% |
Pharmacology, Toxicology and Pharmaceutical Science | 8 | 12% |
Biochemistry, Genetics and Molecular Biology | 6 | 9% |
Agricultural and Biological Sciences | 3 | 5% |
Chemistry | 3 | 5% |
Other | 6 | 9% |
Unknown | 25 | 38% |