液体活检技术在非小细胞肺癌患者EGFR-TKI继发耐药中的应用

doi:10.3969/j.issn.1673-8640.2016.010.001

摘要/Abstract

摘要：

作为非小细胞肺癌治疗史上的里程碑,表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKI）的出现显著延长了非小细胞肺癌患者的生存期,改善了患者的生存质量。亚洲的非小细胞肺癌患者EGFR基因的突变频率远高于白种人,将更加受益于EGFR-TKI药物。然而,分子靶向药物面临的一个重要问题就是耐药。这些最初受益于EGFR-TKI药物的患者,其肿瘤最终都将再次发生进展,并且这种状况往往发生在开始用药后1年左右。由于EGFR-TKI的继发耐药,目前已相继出现了3代EGFR-TKI药物。在众多耐药机制中最受关注的耐药突变就是EGFR T790M和C797S点突变。为了达到更好的治疗效果,必须对使用EGFR-TKI药物的患者进行继发耐药动态监测。组织活检是癌症诊断的金标准,然而组织活检由于存在操作风险较高、组织样本获得困难、无法实时检测及肿瘤异质性等问题,无法对非小细胞肺癌患者进行动态监测。液体活检是一种方便、快捷、具有较高可靠性、新兴的非侵入性检测方法,其通过检测血液中循环肿瘤细胞（CTC）、循环肿瘤DNA（ctDNA）及肿瘤释放出的外泌体,对肿瘤进行早期诊断、筛查、疗效和预后评估以及耐药监测等。文章综述了EGFR-TKI药物及液体活检技术的发展现状,并对液体活检技术在非小细胞肺癌患者EGFR-TKI继发耐药中的应用进行简评和展望。

关键词: 液体活检, 表皮生长因子受体, 酪氨酸激酶抑制剂, 非小细胞肺癌

Abstract:

As a milestone in the treatment of non-small-cell lung cancer,epidermal growth factor receptor （EGFR）-tyrosine kinase inhibitor（TKI） drugs significantly prolong the lifetime of patients with non-small-cell lung cancer and improve the patients' life quality. The frequency of EGFR mutation among non-small-cell lung cancer patients in Asia is higher than that among white men,so Asian patients have more benefits from EGFR-TKI drugs. However,one of the most important problems in targeted drugs is drug resistance. All EGFR-mutated patients who initially benefit from EGFR-TKI drugs develop progressive disease eventually,usually after approximately 1 year since treatment. Nowadays,due to drug resistance,there have been 3 generations of EGFR-TKI drugs. For the mechanisms of EGFR-TKI drug resistance,point mutation EGFR T790M and C797S are of special concern. Dynamic monitoring of drug resistance must be performed in patients who use EGFR-TKI drugs to achieve better therapeutic effect. Pathological biopsy is a gold standard for the diagnosis of cancer. However,pathological biopsy can not be competent for the dynamic monitoring of non-small-cell lung cancer patients,due to the risk of operation,the difficulty of getting tissue samples,being unable to determine in real-time,tumor heterogeneity and so on. Liquid biopsy is a new,non-invasive,convenient and highly reliable determination method. Liquid biopsy shows great potential on early diagnosis and screening,evaluation of therapeutic effect and prognosis and monitoring drug resistance by determing circulating tumor cell（CTC）,circulating tumor DNA（ctDNA）and tumor-released exosome in blood. This article reviews the progress of EGFR-TKI drugs and liquid biopsy,and assesses the potential of liquid biopsy in EGFR-TKI drug resistance of patients with non-small-lung cancer.

Key words: Liquid biopsy, Epidermal growth factor receptor, Tyrosine kinase inhibitor, Non-small-cell lung cancer

中图分类号:

R446.11

林铖, 姜傥. 液体活检技术在非小细胞肺癌患者EGFR-TKI继发耐药中的应用[J]. 检验医学, 2016, 31(10): 835-843.

LIN Cheng, JIANG Tang. Liquid biopsy for monitoring EGFR-TKI drug resistance in patients with non-small-cell lung cancer[J]. Laboratory Medicine, 2016, 31(10): 835-843.

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