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非小细胞肺癌的靶向治疗:聚焦于表皮生长因子受体突变

Targeted therapy in non-small cell lung cancer: a focus on epidermal growth factor receptor mutations.

作者信息

Milano Gérard A

机构信息

Oncopharmacology Unit, Centre Antoine-Lacassagne, 33 avenue de Valombrose, 06189 NICE Cedex 2, France.

出版信息

Chin Clin Oncol. 2015 Dec;4(4):47. doi: 10.3978/j.issn.2304-3865.2015.12.04.

DOI:10.3978/j.issn.2304-3865.2015.12.04
PMID:26730759
Abstract

The main molecular targeting of lung cancer [non-small cell lung cancer (NSCLC)] concerns mutations of epidermal growth factor receptor (EGFR). The awaited responsiveness of tumors carrying these mutations is high with for instance 60% to 80% with tyrosine kinase inhibitors hitting EGFR mutations. The EGFR T790M as a secondary mutation is responsible for the occurrence of a resistance phenomenon. A multitude of drugs have been produced and tested with the property of a specific binding at the EGFR T790M site. There is currently an evolution oriented to a robust genotyping methods allowing the identification of given molecular anomalies (pyrosequencing for instance) towards the consideration of a much larger set of molecular anomalies under the form of a global genotyping realized with the use of next-generation sequencing (NGS). This phase of whole genome analysis necessitates the introduction of a specialized staff for data treatment. A possible substitution plasma/tumor for the mutation analyses is perceptible in lung cancer, a preference being however given to the intratumoral direct investigation when this is feasible. EGFR mutations as targetable anomalies are illustrative examples, that the management of NSCLC is currently drawing a significant benefit from personalized therapy.

摘要

肺癌[非小细胞肺癌(NSCLC)]的主要分子靶向涉及表皮生长因子受体(EGFR)的突变。携带这些突变的肿瘤对酪氨酸激酶抑制剂靶向EGFR突变的预期反应率很高,例如60%至80%。EGFR T790M作为一种继发突变,是耐药现象产生的原因。已经研发并测试了多种具有在EGFR T790M位点特异性结合特性的药物。目前的发展趋势是从强大的基因分型方法(例如焦磷酸测序)来识别特定分子异常,转向以使用下一代测序(NGS)进行的全基因组基因分型形式来考虑更多的分子异常。全基因组分析阶段需要引入专业人员进行数据处理。在肺癌中,可以明显看出用血浆/肿瘤替代进行突变分析,不过在可行的情况下,更倾向于进行肿瘤内直接检测。作为可靶向异常的EGFR突变是典型例子,表明NSCLC的治疗目前正从个性化治疗中显著获益。

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