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 6,8; Nicke, Barbara 6; Schuett, Marion 3,6; Eklund, Aron C.9; Ng, Charlotte 2,6; Li, Qiyuan 9; Hardcastle, Thomas 2,6; Lee, Alvin 6; Roy, Rajat 6; East, Philip 6; Kschischo, Maik 3; Endesfelder, David 3; Wylie, Paul 12; Se, Nyun Kim 11; Chen, Jie Guang 10; Howell, Michael 6; Ried, Thomas 5; Habermann, Jens K.4; Auer, Gert 7; Brenton, James D.6; Szallasi, Zoltan 1,9; Downward, Julian 6
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
卷号	106 期号:21 页码:8671-8676
DOI	10.1073/pnas.0811835106
收录类别	SCOPUS
发表日期	2009-05-26
URL	查看原文
Scopus记录号	2-s2.0-66649137945
自科自定义期刊分类	T3(A)类
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.Harvard-MIT Health Sciences and Technology; 2.University of Cambridge; 3.Fachhochschule Koblenz; 4.Universitätsklinikum Schleswig-Holstein Campus Lübeck; 5.National Cancer Institute (NCI); 6.Cancer Research UK; 7.Karolinska Institutet; 8.Royal Marsden Hospital; 9.Technical University of Denmark; 10.Wenzhou Medical University; 11.Digital Genomics, Inc.; 12.TTP LabTech Ltd.
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.