Research ExplorerPublicationsChromosomal instability determines taxane response

Chromosomal instability determines taxane response

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Chromosomal instability determines taxane response. / Swanton, Charles; Nicke, Barbara; Schuett, Marion; Eklund, Aron C; Ng, Charlotte; Li, Qiyuan; Hardcastle, Thomas; Lee, Alvin; Roy, Rajat; East, Philip; Kschischo, Maik; Endesfelder, David; Wylie, Paul; Kim, Se Nyun; Chen, Jie-Guang; Howell, Michael; Ried, Thomas; Habermann, Jens K; Auer, Gert; Brenton, James D; Szallasi, Zoltan; Downward, Julian.

In: P NATL ACAD SCI USA, Vol. 106, No. 21, 26.05.2009, p. 8671-6.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Swanton, C, Nicke, B, Schuett, M, Eklund, AC, Ng, C, Li, Q, Hardcastle, T, Lee, A, Roy, R, East, P, Kschischo, M, Endesfelder, D, Wylie, P, Kim, SN, Chen, J-G, Howell, M, Ried, T, Habermann, JK, Auer, G, Brenton, JD, Szallasi, Z & Downward, J 2009, 'Chromosomal instability determines taxane response', P NATL ACAD SCI USA, vol. 106, no. 21, pp. 8671-6. https://doi.org/10.1073/pnas.0811835106

APA

Swanton, C., Nicke, B., Schuett, M., Eklund, A. C., Ng, C., Li, Q., Hardcastle, T., Lee, A., Roy, R., East, P., Kschischo, M., Endesfelder, D., Wylie, P., Kim, S. N., Chen, J-G., Howell, M., Ried, T., Habermann, J. K., Auer, G., ... Downward, J. (2009). Chromosomal instability determines taxane response. P NATL ACAD SCI USA, 106(21), 8671-6. https://doi.org/10.1073/pnas.0811835106

Vancouver

Swanton C, Nicke B, Schuett M, Eklund AC, Ng C, Li Q et al. Chromosomal instability determines taxane response. P NATL ACAD SCI USA. 2009 May 26;106(21):8671-6. https://doi.org/10.1073/pnas.0811835106

Bibtex

@article{d2371e3413034d05a9edc585d41687a5,
title = "Chromosomal instability determines taxane response",
abstract = "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.",
keywords = "Bridged-Ring Compounds/pharmacology, Cell Survival/drug effects, Chromosomal Instability/drug effects, Drug Resistance, Neoplasm/drug effects, Female, Gene Expression Regulation, Neoplastic, Humans, Microtubules/metabolism, Neoplasms/genetics, Paclitaxel/toxicity, Polymerase Chain Reaction, Prognosis, Taxoids/pharmacology",
author = "Charles Swanton and Barbara Nicke and Marion Schuett and Eklund, {Aron C} and Charlotte Ng and Qiyuan Li and Thomas Hardcastle and Alvin Lee and Rajat Roy and Philip East and Maik Kschischo and David Endesfelder and Paul Wylie and Kim, {Se Nyun} and Jie-Guang Chen and Michael Howell and Thomas Ried and Habermann, {Jens K} and Gert Auer and Brenton, {James D} and Zoltan Szallasi and Julian Downward",
year = "2009",
month = may,
day = "26",
doi = "10.1073/pnas.0811835106",
language = "English",
volume = "106",
pages = "8671--6",
journal = "P NATL ACAD SCI USA",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "21",

}

RIS

TY - JOUR

T1 - Chromosomal instability determines taxane response

AU - Swanton, Charles

AU - Nicke, Barbara

AU - Schuett, Marion

AU - Eklund, Aron C

AU - Ng, Charlotte

AU - Li, Qiyuan

AU - Hardcastle, Thomas

AU - Lee, Alvin

AU - Roy, Rajat

AU - East, Philip

AU - Kschischo, Maik

AU - Endesfelder, David

AU - Wylie, Paul

AU - Kim, Se Nyun

AU - Chen, Jie-Guang

AU - Howell, Michael

AU - Ried, Thomas

AU - Habermann, Jens K

AU - Auer, Gert

AU - Brenton, James D

AU - Szallasi, Zoltan

AU - Downward, Julian

PY - 2009/5/26

Y1 - 2009/5/26

N2 - 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.

AB - 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.

KW - Bridged-Ring Compounds/pharmacology

KW - Cell Survival/drug effects

KW - Chromosomal Instability/drug effects

KW - Drug Resistance, Neoplasm/drug effects

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Microtubules/metabolism

KW - Neoplasms/genetics

KW - Paclitaxel/toxicity

KW - Polymerase Chain Reaction

KW - Prognosis

KW - Taxoids/pharmacology

U2 - 10.1073/pnas.0811835106

DO - 10.1073/pnas.0811835106

M3 - SCORING: Journal article

C2 - 19458043

VL - 106

SP - 8671

EP - 8676

JO - P NATL ACAD SCI USA

JF - P NATL ACAD SCI USA

SN - 0027-8424

IS - 21

ER -