Mini-reviewEAI045: The fourth-generation EGFR inhibitor overcoming T790M and C797S resistance

- Drug resistance develops rapidly with the tyrosine kinase inhibitor therapy for advanced non-small cell lung cancer.
- Acquired mutations have been found to mediate the resistance.
- New small molecule inhibitors targeting these new mutations are being developed.
- This minireview summarizes the latest development in searching for a novel agent as the fourth generation inhibitor for EGFR.

The third-generation tyrosine kinase inhibitors (TKI), AZD9291 (osimertinib) and CO-1686 (rociletinib) of epidermal growth factor receptor (EGFR) are highly active against T790M positive non-small cell lung cancer (NSCLC). However, resistance develops rapidly. EGFR C797S mutation was reported to be a leading mechanism of resistance to the third-generation inhibitors. The C797S mutation appears to be an ideal target for overcoming the acquired resistance to the third-generation inhibitors. This review summarizes the latest development on the discovery of a fourth-generation EGFR TKI, EAI045.3.