期刊
NEW ENGLAND JOURNAL OF MEDICINE
卷 368, 期 25, 页码 2395-2401出版社
MASSACHUSETTS MEDICAL SOC
DOI: 10.1056/NEJMoa1215530
关键词
-
资金
- Pfizer
- National Cancer Institute [5R01CA164273-02, R01CA137008, Lung SPORE P50CA090578, a1R21CA161590-01]
- V Foundation Translational Research Grant
- Be a Piece of the Solution
- Evan Spirito Memorial Foundation
- Medical Research Council [G0701935, G0902275] Funding Source: researchfish
Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), has also recently shown efficacy in the treatment of lung cancers with ROS1 translocations. Resistance to crizotinib developed in a patient with metastatic lung adenocarcinoma harboring a CD74-ROS1 rearrangement who had initially shown a dramatic response to treatment. We performed a biopsy of a resistant tumor and identified an acquired mutation leading to a glycine-to-arginine substitution at codon 2032 in the ROS1 kinase domain. Although this mutation does not lie at the gatekeeper residue, it confers resistance to ROS1 kinase inhibition through steric interference with drug binding. The same resistance mutation was observed at all the metastatic sites that were examined at autopsy, suggesting that this mutation was an early event in the clonal evolution of resistance.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据