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.

中文翻译：

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获得性奥希替尼耐药机制及克服策略研究进展综述

表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）靶向治疗是晚期 EGFR 突变非小细胞肺癌（NSCLC）的标准一线治疗。以奥希替尼为代表的第三代EGFR-TKI已被批准克服第一代或第二代TKI耐药患者的EGFR T790M突变，为晚期NSCLC患者带来更多生存获益。然而，第三代EGFR-TKI的耐药仍然不可避免。获得性耐药是限制EGFR突变NSCLC患者靶向治疗长期有效性的主要原因。第三代EGFR-TKI耐药机制已成为靶向治疗领域的研究热点。本文综述了晚期NSCLC对奥希替尼耐药机制的研究进展以及潜在的克服策略，希望为NSCLC精准治疗提供临床依据和思路。