循网移动 | 购买点卡 | 卡密充值
网站颜色:
无论是赞助及合作办会、自主办会还是赞助医生参会,它们各自..
究其原因,城市等级医院(指地级以上城市的二、三级医院,含..
掉出2016-2017南方所百强榜的企业有: 长春高新 亚宝药业 ..
循环卫生

EGFR独立的 AZD9291耐药机制
2017-06-15 10:47:23 来源: 作者: 【 】 浏览:8次 评论:0
简述:AZD9291耐药产生2类不同病例:her2和met扩增。有趣的是发生T790M突变的完全消失,在一个病例中,通过组织活检发现原发部位发生T790M突变而转移部位出现不同信号通路而产生耐药。建议联合her2或met抑制剂用药。
责任编辑:admin


研究发现 AZD9291耐药产生2类不同病例:her2和met扩增。有趣的是发生T790M突变的完全消失,在一个病例中,通过组织活检发现原发部位发生T790M突变而转移部位出现不同信号通路而产生耐药。建议联合her2或met抑制剂用药。

EGFR-independent mechanisms of acquired resistance to AZD9291 in EGFR T790M-positive NSCLC patients.

Abstract

BACKGROUND:

AZD9291 is an oral, irreversible, mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKI), which specifically targets both sensitizing and resistant T790M mutations. This compound has shown outstanding activity, in a phase I/II (AURA) trial. However, despite impressive tumor responses in T790M-positive patients, acquired resistance to this drug limits the benefit of this compound. Mutations at the EGFR C797 codon, located within the kinase-binding site, were very recently reported to be a potential mechanism of resistance to AZD9291 in T790M-positive patients.

PATIENTS AND METHODS:

To identify potential mechanisms of resistance to AZD9291, we report here on two patients with resistant biopsy specimens that had been treated with AZD9291.

RESULTS:

We identified in two distinct cases, HER2 and MET amplification by FISH and CGH as a potential mechanism of acquired resistance to third-generation EGFR-TKI. Interestingly, this event occurred with complete loss of the T790M mutation. In one case, we observed a different molecular status at two biopsy sites (the T790M mutation at the primary site and wild-type T790M at the metastatic site with different pathways of acquired resistance to AZD9291).

CONCLUSION:

Our observations suggest that T790M-positive and wild-type T790M clones may coexist at baseline. AZD9291 efficiently suppresses the growth of T790M-positive cells, but a population of wild-type T790M cells at baseline will mediate the development of resistance, here via a by-pass pathway activating either HER2 or MET.

您看到此篇文章时的感受是:
】【打印繁体】【投稿】 【收藏】 【推荐】 【举报】 【评论】 【关闭】【返回顶部

1、凡标注“原创” 的所有作品,版权均属于县域医疗卫生市场研究中心,未经本网授权,任何单位及个人不得转载、摘编或以其它方式使用上述作品。已经本网授权使用作品的,应在授权范围内使用,并注明“县域医疗卫生市场研究中心”。违反上述声明者,本网将追究其相关法律责任。

2、凡本网注明 “来源:XXX” 的作品,均转载自其它媒体,转载目的在于传递更多信息,并不代表本网赞同其观点和对其真实性负责。如因作品内容、版权和其它问题需要同本网联系的,请在30日内进行。 021-60526838

我来说两句
帐  号: 密码: (新用户注册)
验 证 码:
表 情:
内  容:

《医药营销拾日谈》2016年度合订本(包邮)

120

446人购买