北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学首钢医院  > 普通外科  > 期刊论文
学科主题: 临床医学
题名:
Positive feedback between oncogenic KRAS and HIF-1 alpha confers drug resistance in colorectal cancer
作者: Wang, Yanzhao1; Lei, Fuming2; Rong, Wanshui2; Zeng, Qingmin2; Sun, Wenbing1
关键词: combination therapy ; EGFR inhibitor resistance ; KRAS G12V
刊名: ONCOTARGETS AND THERAPY
发表日期: 2015
DOI: 10.2147/OTT.S80017
卷: 8, 页:1229-1237
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biotechnology & Applied Microbiology ; Oncology
研究领域[WOS]: Biotechnology & Applied Microbiology ; Oncology
关键词[WOS]: HYPOXIA-INDUCIBLE FACTOR-1-ALPHA ; MULTICENTER PHASE-II ; MUTATION ; THERAPY ; INHIBITORS ; CETUXIMAB ; EFFICACY ; PX-478 ; STRATEGIES ; MECHANISM
英文摘要:

Approximately 30%-50% of colorectal cancers (CRCs) harbor the somatic mutated KRAS gene. KRAS G12V, one of the most common KRAS mutations in CRCs, is linked to increased tumor aggressiveness, less response to anti-epidermal growth factor receptor (EGFR) therapy, and poor survival rate. In this study, we sought to determine whether resistance to EGFR inhibitors in colorectal cancer cells harboring KRAS G12V mutation is associated with hypoxia. Our data indicated that HIF-1 alpha was induced by KRAS G12V signaling at transcription level. Hypoxia or HIF-1 alpha overexpression could increase KRAS G12V activity. Therefore, a positive feedback between hypoxia and KRAS G12V activation was formed. Cetuximab, an EGFR inhibitor, which has a minor effect on KRAS-mutant CRCs, could effectively inhibit the proliferation of CRC cells harboring KRAS G12V mutation when combined with HIF-1 alpha inhibitor PX-478. Our data indicated that hypoxia was involved in resistance to anti-EGFR therapy, and a combination therapy might be necessary for CRC patients with KRAS mutation.

语种: 英语
所属项目编号: 30872490 ; 81172320 ; 32067501207
项目资助者: National Natural Science Foundation of China ; Dr Jieping Wu Medical Foundation
WOS记录号: WOS:000355120000001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51362
Appears in Collections:北京大学首钢医院_普通外科_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Capital Med Univ, Beijing Chao Yang Hosp, Dept Hepatobiliary Surg, Beijing 10043, Peoples R China
2.Peking Univ, Shougang Hosp, Dept Gen Surg, Beijing 100871, Peoples R China

Recommended Citation:
Wang, Yanzhao,Lei, Fuming,Rong, Wanshui,et al. Positive feedback between oncogenic KRAS and HIF-1 alpha confers drug resistance in colorectal cancer[J]. ONCOTARGETS AND THERAPY,2015,8:1229-1237.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Wang, Yanzhao]'s Articles
[Lei, Fuming]'s Articles
[Rong, Wanshui]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Wang, Yanzhao]‘s Articles
[Lei, Fuming]‘s Articles
[Rong, Wanshui]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace