Clinical Management and Drug Resistance in EGFR-Mutant Lung Cancer

EGFR-mutant non-small cell lung cancer is more common in Asian populations. EGFR is critically involved in lung adenocarcinoma development.EGFR-targeted therapy has greatly improved patient survival. Therefore, EGFR- mutant NSCLC has become one of the models for precision oncology. Osimertinib is a third-generation EGFR tyrosine kinase inhibitor. It irreversibly binds to the cysteine residue at position 797 of the EGFR protein, selectively inhibits common EGFR activating mutations, and overcomes the classic T790M drug-resistant mutation. In addition, Osimertinib has good central nervous system permeability. Clinical trials demonstrate that osimertinib significantly prolongs progression-free survival and overall survival. These benefits are reflected in the initial and subsequent management of EGFR mutant NSCLC. The scope of application of osimertinib has been extended to adjuvant treatment and neoadjuvant therapy, which confirms its core role in disease management. However, with the wide application of osimertinib, acquired drug resistance has become a major clinical problem. Its potential mechanism is more diverse and complex than the earlier-generation EGFR-TKIs. This paper reviews the molecular activity basis of EGFR signaling pathway and osimertinib, and reviews its latest progress in clinical application. Finally, this paper discusses the mechanism of EGFR dependence and EGFR non-dependent drug resistance, aiming to provide insights into precision treatment strategies of EGFR mutant NSCLC.