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致癌性 MET 作为 EGFR 抑制剂耐药的非小细胞肺癌的有效治疗靶点:凤凰涅槃。

Oncogenic MET as an Effective Therapeutic Target in Non-Small Cell Lung Cancer Resistant to EGFR Inhibitors: The Rise of the Phoenix.

机构信息

Laboratory of Translational Cancer Medicine, Candiolo Cancer Institute IRCCS, and Department of Oncology, University of Torino School of Medicine, Candiolo, Torino, Italy.

出版信息

Cancer Discov. 2016 Dec;6(12):1306-1308. doi: 10.1158/2159-8290.CD-16-1181.

Abstract

Anecdotal reports have shown that concomitant inhibition of EGFR and MET can be clinically effective in patients with non-small cell lung cancer carrying EGFR mutations and MET amplification, but large phase III trials in genetically unselected individuals have failed to confirm the benefit of this combination therapy. A new study corroborates the evidence that lung cancer susceptibility to EGFR and MET blockade is sustained by genetically based activation of both targets and identifies a mutation in MET that confers acquired resistance to standard MET inhibitors hitting the active kinase, yet is vulnerable to other MET-directed compounds with a different binding mode. Cancer Discov; 6(12); 1306-8. ©2016 AACR.See related article by Bahcall and colleagues, p. 1334.

摘要

已有报道显示,针对携带 EGFR 突变和 MET 扩增的非小细胞肺癌患者,同时抑制 EGFR 和 MET 可获得临床疗效,但在未进行基因选择的患者中进行的大型 III 期临床试验未能证实这种联合治疗的获益。一项新研究证实了这样的证据,即肺癌对 EGFR 和 MET 阻断的敏感性是由这两个靶点的基因激活所维持的,并确定了 MET 中的一个突变,该突变导致对标准 MET 抑制剂(靶向激酶的活性形式)产生获得性耐药,但易受其他具有不同结合模式的靶向 MET 的化合物影响。Cancer Discov; 6(12); 1306-8. ©2016 AACR. 请参阅 Bahcall 及其同事的相关文章,第 1334 页。

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