Mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer
Mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer
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DOI：
10.1158/1078-0432.ccr-07-2248
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发表时间：
2008-05-15
影响因子：
11.5
通讯作者：
Jaenne, Pasi A.
中科院分区：
文献类型：
--
作者：
Engelman, Jeffrey A.;Jaenne, Pasi A.
表皮生长因子受体 (EGFR) 酪氨酸激酶抑制剂吉非替尼和厄洛替尼是治疗 EGFR 体细胞突变的非小细胞肺癌患者的有效疗法。然而，所有患者最终都会对这些药物产生耐药性。因此，非常需要了解患者如何产生耐药性，以开发针对这些癌症的有效疗法。过去几年的研究已经确定了两种不同的 EGFR 酪氨酸激酶抑制剂耐药机制：EGFR 二次突变（EGFR 790M）和 MET 癌基因扩增。这些发现导致了使用新设计的靶向疗法进行临床试验，这些疗法可以克服这些耐药机制，并在实验室研究中显示出希望。正在进行的研究工作可能会继续确定其他耐药机制，这些发现有望转化为非小细胞肺癌患者的有效疗法。
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors gefitinib and erlotinib are effective therapies for non-small cell lung cancer patients whose tumors harbor somatic mutations in EGFR. All patients, however, ultimately develop resistance to these agents. Thus, there is a great need to understand how patients become resistant to develop effective therapies for these cancers. Studies over the last few years have identified two different EGFR tyrosine kinase inhibitor resistance mechanisms, a secondary mutation in EGFR, EGFR 790M, and amplification of the MET oncogene. These findings have led to clinical trials using newly designed targeted therapies that can overcome these resistance mechanisms and have shown promise in laboratory studies. Ongoing research efforts will likely continue to identify additional resistance mechanisms, and these findings will hopefully translate into effective therapies for non - small cell lung cancer patients.