|Title:||Update on recent preclinical and clinical studies of T790M mutant-specific irreversible epidermal growth factor receptor tyrosine kinase inhibitors||Authors:||Liao, Bin-Chi
Yang, James Chih-Hsin
|Keywords:||Non-small cell lung cancer;Epidermal growth factor receptor;Tyrosine kinase inhibitor;T790M mutation;Osimertinib;Rociletinib;Olmutinib;EGF816;ASP8273||Issue Date:||2016||Start page/Pages:||86||Source:||Journal of Biomedical Science||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.
|Appears in Collections:||醫學系|
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