dgytzyeq
发表于 2015-12-12 06:47:35
多谢整理、分享成果。
等待春天
发表于 2015-12-13 08:41:53
老马辛苦了，多谢分享，给你点赞了。
lxd0123
发表于 2016-2-2 23:15:22
Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models.
Resistance to targeted EGFR inhibitors is likely to develop in EGFR-mutant lung cancers. Early identification of innate or acquired resistance mechanisms to these agents is essential to direct development of future therapies. We describe the detection of heterogeneous mechanisms of resistance within populations of EGFR-mutant cells (PC9 and/or NCI-H1975) with acquired resistance to current and newly developed EGFR tyrosine kinase inhibitors, including AZD9291. We report the detection of NRAS mutations, including a novel E63K mutation, and a gain of copy number of WT NRAS or WT KRAS in cell populations resistant to gefitinib, afatinib, WZ4002, or AZD9291. Compared with parental cells, a number of resistant cell populations were more sensitive to inhibition by the MEK inhibitor selumetinib (AZD6244; ARRY-142886) when treated in combination with the originating EGFR inhibitor. In vitro, a combination of AZD9291 with selumetinib prevented emergence of resistance in PC9 cells and delayed resistance in NCI-H1975 cells. In vivo, concomitant dosing of AZD9291 with selumetinib caused regression of AZD9291-resistant tumors in an EGFRm/T790M transgenic model. Our data support the use of a combination of AZD9291 with a MEK inhibitor to delay or prevent resistance to AZD9291 in EGFRm and/or EGFRm/T790M tumors. Furthermore, these findings suggest that NRAS modifications in tumor samples from patients who have progressed on current or EGFR inhibitors in development may support subsequent treatment with a combination of EGFR and MEK inhibition.
Cancer research2015年75卷12期 2489-500页
lxd0123
发表于 2016-2-4 12:35:59
本帖最后由 lxd0123 于 2016-2-4 12:43 编辑
文章在这
lxd0123
发表于 2016-2-4 13:00:54
这篇文章主要还是说了RAS–MAPK通路是一种9291耐药的逃逸机制，但需要建立一种检查机制筛选出收益人群，主要还是通过联合6244
ljgzj1999913
发表于 2016-2-26 17:42:11
谢谢老马，学习中
xuwd668
发表于 2016-4-27 17:49:37
谈何容易
发表于 2016-6-12 14:20:23
感谢楼主及大家的经验分享！
wxh110
发表于 2016-7-21 02:14:05
我能利用数据库，为大家提供一些有关的文献
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