Update on recent preclinical and clinical studies of T790M mutant-specific irreversible epidermal growth factor receptor tyrosine kinase inhibitors

Journal of Biomedical Science

Review

Jih-Hsiang Lee¹  Chia-Chi Lin²  Bin-Chi Liao³  James Chih-Hsin Yang⁴ 

[1] Department of Oncology, National Taiwan University Hospital, 7, Chung-Shan South Road, 100, Taipei, Taiwan;Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan;Department of Oncology, National Taiwan University Hospital, 7, Chung-Shan South Road, 100, Taipei, Taiwan;Department of Urology, College of Medicine, National Taiwan University, Taipei, Taiwan;Department of Oncology, National Taiwan University Hospital, 7, Chung-Shan South Road, 100, Taipei, Taiwan;National Taiwan University Cancer Center, College of Medicine, National Taiwan University, Taipei, Taiwan;Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan;Department of Oncology, National Taiwan University Hospital, 7, Chung-Shan South Road, 100, Taipei, Taiwan;National Taiwan University Cancer Center, College of Medicine, National Taiwan University, Taipei, Taiwan;Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan;Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan;

关键词: Non-small cell lung cancer;    Epidermal growth factor receptor;    Tyrosine kinase inhibitor;    T790M mutation;    Osimertinib;    Rociletinib;    Olmutinib;    EGF816;    ASP8273;   

DOI  :  10.1186/s12929-016-0305-9

 received in 2016-08-19, accepted in 2016-11-03,  发布年份 2016

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s). 2016