Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai, 200032, People's Republic of China.
Department of Thoracic Surgery, Xuhui District Center Hospital of Shanghai, Shanghai, 200031, China.
Clin Transl Oncol. 2019 Oct;21(10):1287-1301. doi: 10.1007/s12094-019-02075-1. Epub 2019 Mar 12.
Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) represents a paradigm shift in the treatment of non-small cell lung cancer (NSCLC) patients and has been the first-line therapy in clinical practice. While erlotinib, gefitinib and afatinib have achieved superior efficacy in terms of progression-free survival and overall survival compared with conventional chemotherapy in NSCLC patients, most people inevitably develop acquired resistance to them, which presents another challenge in the treatment of NSCLC. The mechanisms of acquired resistance can be classified as three types: target gene mutation, bypass signaling pathway activation and histological transformation. And the most common mechanism is T790M which accounts for approximately 50% of all subtypes. Many strategies have been explored to overcome the acquired resistance to EGFR TKI. Continuation of EGFR TKI beyond progressive disease is confined to patients in asymptomatic stage when the EGFR addiction is still preserved in some subclones. While the combination of EGFR TKI and chemotherapy or other targeted agents has improved the survival benefit in EGFR TKI resistant patients, there are controversies within them. The next-generation EGFR TKI and immunotherapy represent two novel directions for overcoming acquired resistance and have achieved promising efficacy. Liquid biopsy provides surveillance of the EGFR mutation by disclosing the entire genetic landscape but tissue biopsy is still indispensable because of the considerable rate of false-negative plasma.
表皮生长因子受体酪氨酸激酶抑制剂 (EGFR TKI) 代表了非小细胞肺癌 (NSCLC) 治疗领域的范式转变，已成为临床实践中的一线治疗方法。厄洛替尼、吉非替尼和阿法替尼在无进展生存期和总生存期方面优于 NSCLC 患者的传统化疗，然而，大多数人不可避免地会对它们产生获得性耐药，这给 NSCLC 的治疗带来了另一个挑战。获得性耐药的机制可分为三种类型：靶基因突变、旁路信号通路激活和组织学转化。最常见的机制是 T790M，约占所有亚型的 50%。已经探索了许多策略来克服 EGFR TKI 的获得性耐药。在 EGFR 依赖性在某些亚克隆中仍然存在的情况下，继续使用 EGFR TKI 治疗进展期疾病仅限于无症状阶段的患者。EGFR TKI 与化疗或其他靶向药物联合应用改善了 EGFR TKI 耐药患者的生存获益，但其中存在争议。下一代 EGFR TKI 和免疫疗法代表了克服获得性耐药的两个新方向，已取得了有希望的疗效。液体活检通过揭示整个遗传图谱来监测 EGFR 突变，但由于血浆假阴性率相当高，组织活检仍然不可或缺。
