文章摘要

活化的RET和ROS：肺腺癌新的驱动基因

作者: 1Bos Marc, 2Gardizi Masyar, 2Schidhaus Hans-Ulrich, 2Buettner Reinhard, 1Wolf Juergen
1 Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany; 2. Center for Integrated Oncology Cologne/Bonn, Germany
2 Center for Integrated Oncology Cologne/Bonn, Germany; 3. Institute of Pathology, University Hospital Cologne, Cologne, Germany
通讯: Wolf Juergen Email: juergen.wolf@uk-koeln.de
DOI: 10.3978/j.issn.2095-6959.2014.02.001

摘要

ROS1和RET的基因重排是新发现的肺腺癌驱动基因，各自突变频率约为1%。肺腺癌中RET和ROS1基因重排与其他已知的驱动基因几乎没有重叠，成为独立的新的肺腺癌分子亚型。肺腺癌中ROS1和RET突变基因的临床病理学特征已经阐明，体外实验也证实数种多靶点受体激酶抑制剂能抑制含ROS1和RET突变基因的非小细胞肺癌(non-small cell lung cancer，NSCLC)细胞系。而临床研究显示MET/ALK/ROS抑制剂克唑替尼在ROS1突变阳性的肺癌患者中疗效显著。目前，正开展一些针对肺腺癌ROS1和RET基因的各种激酶抑制剂的早期临床试验。针对这些基因突变的新的肺腺癌亚群的个体化治疗极有可能在不久的将来作为常规的临床治疗措施。
关键词： 肺癌；腺癌；RET；ROS

Activated RET and ROS: two new driver mutations in lung adenocarcinoma

Authors: 1Marc Bos, 2Masyar Gardizi, 2Hans-Ulrich Schidhaus, 2Reinhard Buettner, 1Juergen Wolf
1 Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany; 2. Center for Integrated Oncology Cologne/Bonn, Germany; 3. Institute of Pathology, University Hospital Cologne, Cologne, Germany
2 Center for Integrated Oncology Cologne/Bonn, Germany; 3. Institute of Pathology, University Hospital Cologne, Cologne, Germany

CorrespondingAuthor: Juergen Wolf Email: juergen.wolf@uk-koeln.de

DOI: 10.3978/j.issn.2095-6959.2014.02.001

Abstract

Rearrangements of ROS1 and RET have been recently described as new driver mutations in lung adenocarcinoma with a frequency of about 1% each. RET and ROS1 rearrangements both represent unique molecular subsets of lung adenocarcinoma with virtually no overlap with other known driver mutations described so far in lung adenocarcinoma. Specific clinicopathologic characteristics have been described and several multitargeted receptor kinase inhibitors have shown in vitro activity against NSCLC cells harbouring these genetic alterations. In addition, the MET/ALK/ROS inhibitor crizotinib has already shown impressive clinical activity in patients with advanced ROS1-positive lung cancer. Currently, several early proof of concept clinical trials are testing various kinase inhibitors in both molecular subsets of lung adenocarcinoma patients. Most probably, personalized treatment of these genetically defined new subsets of lung adenocarcinoma will be implemented in routine clinical care of lung cancer patients in the near future.

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