文章：

合理的、基于生物学的EGFR突变的非小细胞肺癌治疗

Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer

原文发布日期：2010-10-22

DOI: 10.1038/nrc2947

类型: Review Article

开放获取: 否

要点：

1. Epidermal growth factor receptor (EGFR)-mutant tumours define a unique subset of non-small-cell lung cancer (NSCLC). These tumours display sensitivity to small-molecule EGFR tyrosine kinase inhibitors (TKIs).
2. Prospective clinical trials have now validated the correlation between EGFR mutation and TKI sensitivity.
3. Multiple mechanisms of primary and secondary resistance of lung tumours to EGFR TKIs have been elucidated.
4. Unfortunately, all patients eventually develop acquired resistance. Secondary mutations in EGFR and/or amplification of the gene encoding the MET receptor tyrosine kinase account for most cases of resistance.
5. On the basis of promising preclinical data, many new rationally designed strategies are now being pursued in clinical trials to overcome acquired resistance.
6. EGFR-mutant lung cancer can serve as a model for other cancers driven by oncogenic kinases.

要点翻译：

1. 表皮生长因子受体（EGFR）突变肿瘤界定了非小细胞肺癌（NSCLC）中一个独特的亚型。这类肿瘤对小分子EGFR酪氨酸激酶抑制剂（TKIs）表现出敏感性。
2. 前瞻性临床试验现已证实EGFR突变与TKI敏感性之间的关联。
3. 肺癌对EGFR TKI原发性及继发性耐药的多重机制已被阐明。
4. 遗憾的是，所有患者最终都会产生获得性耐药。大部分耐药病例由EGFR继发突变和/或编码MET受体酪氨酸激酶的基因扩增引起。
5. 基于前景广阔的临床前数据，目前正在临床试验中探索多种新型理性设计的策略以克服获得性耐药。
6. EGFR突变肺癌可作为其他由致癌激酶驱动的癌症研究模型。

英文摘要：

Epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) was first recognized in 2004 as a distinct, clinically relevant molecular subset of lung cancer. The disease has been the subject of intensive research at both the basic scientific and clinical levels, becoming a paradigm for how to understand and treat oncogene-driven carcinomas. Although patients with EGFR-mutant tumours have increased sensitivity to tyrosine kinase inhibitors (TKIs), primary and acquired resistance to these agents remains a major clinical problem. This Review summarizes recent developments aimed at treating and ultimately curing the disease.

摘要翻译： 

表皮生长因子受体（EGFR）突变型非小细胞肺癌（NSCLC）于2004年首次被确认为一种具有临床意义的独特分子亚型肺癌。该疾病已成为基础与临床层面研究的焦点，成为理解及治疗癌基因驱动型肿瘤的典范。尽管EGFR突变患者对酪氨酸激酶抑制剂（TKIs）具有更高敏感性，但原发性和获得性耐药仍是主要临床难题。本综述总结了旨在治疗并最终治愈该疾病的最新进展。

原文链接：

Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer