Mechanisms of resistance to EGFR tyrosine kinase inhibitors.
Mechanisms of resistance to EGFR tyrosine kinase inhibitors.
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DOI：
10.1016/j.apsb.2015.07.001
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发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Fu L
中科院分区：
文献类型：
--
作者：
Huang L;Fu L
自从发现非小细胞肺癌（NSCLC）是由表皮生长因子受体（EGFR）突变驱动以来，EGFR酪氨酸激酶抑制剂（EGFR- tkis，如吉非替尼和埃洛替尼）已被有效地用于临床治疗。然而，患者最终会产生耐药性。由于多种机制，对EGFR-TKIs的耐药性是不可避免的，如继发性突变（T790M）、替代途径（c-Met、HGF、AXL）的激活、下游途径的异常（K-RAS突变、PTEN的缺失）、EGFR-TKIs介导的凋亡途径的损伤（bcl2样11/BIM缺失多态性）、组织学转化、ATP结合盒（ABC）转运体积液等。在此，我们回顾和总结了已知的EGFR-TKIs耐药机制，并为开发新的治疗策略提供了潜在的靶点。我们回顾和总结了已知的EGFR-TKIs耐药机制，并为开发新的治疗策略提供了潜在的靶点。
Since the discovery that non-small cell lung cancer (NSCLC) is driven by epidermal growth factor receptor (EGFR) mutations, the EGFR tyrosine kinase inhibitors (EGFR-TKIs, e.g., gefitinib and elrotinib) have been effectively used for clinical treatment. However, patients eventually develop drug resistance. Resistance to EGFR-TKIs is inevitable due to various mechanisms, such as the secondary mutation (T790M), activation of alternative pathways (c-Met, HGF, AXL), aberrance of the downstream pathways (K-RAS mutations, loss of PTEN), impairment of the EGFR-TKIs-mediated apoptosis pathway (BCL2-like 11/BIM deletion polymorphism), histologic transformation, ATP binding cassette (ABC) transporter effusion, etc. Here we review and summarize the known resistant mechanisms to EGFR-TKIs and provide potential targets for development of new therapeutic strategies. We review and summarize the known resistant mechanisms to EGFR-TKIs and provide potential targets for development of new therapeutic strategies.