Chromosomal instability determines taxane response

doi:10.1073/pnas.0811835106

科研成果详情

题名	Chromosomal instability determines taxane response
作者	Swanton, Charles 1,2; Nicke, Barbara 1; Schuett, Marion 1,3; Eklund, Aron C.4; Ng, Charlotte 5,6; Li, Qiyuan 4; Hardcastle, Thomas 5,6; Lee, Alvin 1; Roy, Rajat 1; East, Philip 1; Kschischo, Maik 3; Endesfelder, David 3; Wylie, Paul 7; Se, Nyun Kim 8; Chen, Jie-Guang9; Howell, Michael 1; Ried, Thomas 10; Habermann, Jens K.11; Auer, Gert 12; Brenton, James D.5; Szallasi, Zoltan 4,13; Downward, Julian 1
发表日期	2009-05-26
发表期刊	Proceedings of the National Academy of Sciences of the United States of America 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Chemotherapy Drug resistance
摘要	Microtubule-stabilizing (MTS) agents, such as taxanes, are important chemotherapeutics with a poorly understood mechanism of action. We identified a set of genes repressed in multiple cell lines in response to MTS agents and observed that these genes are overexpressed in tumors exhibiting chromosomal instability (CIN). Silencing 22/50 of these genes, many of which are involved in DNA repair, caused cancer cell death, suggesting that these genes are involved in the survival of aneuploid cells. Overexpression of these "CIN- survival" genes is associated with poor outcome in estrogen receptor-positive breast cancer and occurs frequently in basal-like and Her2-positive cases. In diploid cells, but not in chromosomally unstable cells, paclitaxel causes repression of CIN-survival genes, followed by cell death. In the OV01 ovarian cancer clinical trial, a high level of CIN was associated with taxane resistance but carboplatin sensitivity, indicating that CIN may determine MTS response in vivo. Thus, pretherapeutic assessment of CIN may optimize treatment stratification and clinical trial design using these agents.
资助项目	National Cancer Institute[P50CA089393];
ISSN	0027-8424
EISSN	0027-8424
卷号	106 期号:21 页码:8671-8676
DOI	10.1073/pnas.0811835106
收录类别	SCOPUS
URL	查看原文
PubMed ID	19458043
SCOPUSEID	2-s2.0-66649137945
自科自定义期刊分类	T3(A)类
通讯作者地址	[Brenton J. D.]Cancer Research UK,Cambridge Research Institute,Li Ka Shing Centre,United Kingdom
Scopus学科分类	Multidisciplinary
TOP期刊	TOP期刊
引用统计	被引频次：195[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/97553
专题	温州医科大学
作者单位	1.Cancer Research UK,London Research Institute,United Kingdom; 2.Royal Marsden Hospital,Department of Medicine,United Kingdom; 3.University of Applied Sciences Koblenz,RheinAhrCampus,Germany; 4.Center for Biological Sequence Analysis,Technical University of Denmark,Denmark; 5.Cancer Research UK,Cambridge Research Institute,Li Ka Shing Centre,United Kingdom; 6.Department of Oncology,University of Cambridge,United Kingdom; 7.TTP LabTech Ltd.,United Kingdom; 8.Digital Genomics Inc.,South Korea; 9.Wenzhou Medical College,China; 10.Genetics Branch,National Cancer Institute,National Institutes of Health,United States; 11.University Hospital Schleswig-Holstein,Campus Lübeck,Department of Surgery,Germany; 12.Karolinska Institutet,Sweden; 13.Children's Hospital Informatics Program,Harvard-MIT Division of Health Sciences and Technology,Harvard Medical School,United States
推荐引用方式 GB/T 7714	Swanton, Charles,Nicke, Barbara,Schuett, Marion,et al. Chromosomal instability determines taxane response[J]. Proceedings of the National Academy of Sciences of the United States of America,2009,106(21):8671-8676.
APA	Swanton, Charles., Nicke, Barbara., Schuett, Marion., Eklund, Aron C.., Ng, Charlotte., ... & Downward, Julian. (2009). Chromosomal instability determines taxane response. Proceedings of the National Academy of Sciences of the United States of America, 106(21), 8671-8676.
MLA	Swanton, Charles,et al."Chromosomal instability determines taxane response".Proceedings of the National Academy of Sciences of the United States of America 106.21(2009):8671-8676.