New strategies in overcoming acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in lung cancer.
New strategies in overcoming acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in lung cancer.
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DOI：
10.1158/1078-0432.ccr-10-2571
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发表时间：
2011-09-01
期刊：
影响因子：
--
通讯作者：
Pao W
中科院分区：
文献类型：
--
作者：
Oxnard GR;Arcila ME;Chmielecki J;Ladanyi M;Miller VA;Pao W
非小细胞肺癌（NSCLC）的治疗已经被观察到，EGFR突变的肺腺癌对EGFR酪氨酸激酶抑制剂（TKIs）非常敏感。在这些患者中，对EGFR-TKI的获得性耐药中位数为10-14个月，此时，目前的标准做法是转向传统的细胞毒性化疗。已经确定了几种可能的获得性耐药机制，最常见的是在超过50%的病例中发生EGFR T790M看门人突变。在这篇综述中，我们讨论了egfr突变肺癌获得性TKI耐药的最新进展，并回顾了第二代TKI和联合靶向治疗的治疗进展。
The management of non-small cell lung cancer (NSCLC) has been transformed by the observation that lung adenocarcinomas harboring mutations in EGFR are uniquely sensitive to EGFR tyrosine kinase inhibitors (TKIs). In these patients, acquired resistance to EGFR-TKI develops after a median of 10-14 months, at which time the current standard practice is to switch to conventional cytotoxic chemotherapy. Several possible mechanisms for acquired resistance have been identified, the most common being the development of an EGFR T790M gate-keeper mutation in over 50% of cases. In this review, we discuss recent advances in the understanding of acquired TKI resistance in EGFR-mutant lung cancer and review therapeutic progress with second generation TKIs and combinations of targeted therapies.