A review of research progress on mechanisms and overcoming strategies of acquired osimertinib resistance

Targeted therapy with epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs) is the standard first-line treatment for advanced EGFR-mutated non-small cell lung cancer (NSCLC). Third-generation EGFR-TKIs, represented by osimertinib, have been approved to overcome the EGFR T790M mutation in patients who are resistant to first- or second-generation TKIs, which brings more survival benefits for patients with advanced NSCLC. However, resistance to the third generation of EGFR-TKIs is still inevitable. Acquired drug resistance is the main reason for limiting the long-term effectiveness of targeted therapy in EGFR-mutated NSCLC patients. The mechanism of EGFR-TKI resistance of the third generation has become a focus of research in the field of targeted therapy. In this review, we summarize the research progress in resistance mechanisms of advanced NSCLC to osimertinib and the potential overcoming strategies and hope to provide a clinical basis and ideas for precision treatment of NSCLC.