表皮生长因子受体敏感突变肺癌靶向治疗原发耐药的机制及临床对策

针对伴有表皮生长因子受体（EGFR）敏感突变的非小细胞肺癌，基于小分子抑制剂的靶向治疗在临床上取得了极大成效，但仍面临着原发耐药/不敏感的问题。初始治疗的有效比例及疗效深度决定了患者的远期生存。本文梳理了关于原发耐药的主要机制，包括突变亚型结构、原发T790M、合并突变、免疫状态等的影响及其相互关系，以及目前有效药物的证据，提出了多基因分型、精准靶向、“鸡尾酒”疗法等克服原发耐药的管理策略，并展望了该领域的发展趋势，为同行们的临床实践及科研方向提供思路。

Mechanism and Management of Primary Resistance to Targeted Therapy in NSCLC Patients Harboring EGFR Sensitive Mutations

Clinical evidence has showed that targeted therapy with small molecule inhibitors produces good efficacy in patients with non-small cell lung cancer（NSCLC）harboring epidermal growth factor receptor（EGFR）sensitive mutations，but there are also some patients who display primary resistance or insensitivity to the therapy.As the response rate and level to the initial therapy are determinants for patients'long-term survival，we reviewed evidence about major mechanisms leading to primary resistance，including the impact of the structure of EGFR mutation subtypes，primary EGFR T790M mutation，concurrent EGFR mutations，and immune status on the therapy response，as well as their associations，then proposed targeted management strategies，such as treatment targeting the genetic mutation or the mutation site，precise targeted therapy，cocktail therapy and so on，and evaluated the development trend of treatment for primary resistance to targeted therapy.All these aimed at helping medical workers with clinical practice and research.