In vitro analysis of ovarian cancer response to cisplatin, carboplatin, and paclitaxel identifies common pathways that are also associated with overall patient survival

E Bicaku; Y Xiong; D C Marchion; H S Chon; X B Stickles; N Chen; P L Judson; A Hakam; J Gonzalez-Bosquet; R M Wenham; S M Apte; W Fulp; C L Cubitt; D-T Chen; J M Lancaster

doi:10.1038/bjc.2012.207

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In vitro analysis of ovarian cancer response to cisplatin, carboplatin, and paclitaxel identifies common pathways that are also associated with overall patient survival

Journal article

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In vitro analysis of ovarian cancer response to cisplatin, carboplatin, and paclitaxel identifies common pathways that are also associated with overall patient survival

E Bicaku, Y Xiong, D C Marchion, H S Chon, X B Stickles, N Chen, P L Judson, A Hakam, J Gonzalez-Bosquet, R M Wenham, …

British journal of cancer, Vol.106(12), pp.1967-1975

06/05/2012

DOI: 10.1038/bjc.2012.207

PMCID: PMC3388569

PMID: 22596241

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Abstract

Carboplatin and cisplatin, alone or in combination with paclitaxel, have similar efficacies against ovarian cancer (OVCA) yet exhibit different toxicity profiles. We characterised the common and unique cellular pathways that underlie OVCA response to these drugs and analyse whether they have a role in OVCA survival. Ovarian cancer cell lines (n=36) were treated with carboplatin, cisplatin, paclitaxel, or carboplatin-paclitaxel (CPTX). For each cell line, IC(50) levels were quantified and pre-treatment gene expression analyses were performed. Genes demonstrating expression/IC(50) correlations (measured by Pearson; P<0.01) were subjected to biological pathway analysis. An independent OVCA clinico-genomic data set (n=142) was evaluated for clinical features associated with represented pathways. Cell line sensitivity to carboplatin, cisplatin, paclitaxel, and CPTX was associated with the expression of 77, 68, 64, and 25 biological pathways (P<0.01), respectively. We found three common pathways when drug combinations were compared. Expression of one pathway ('Transcription/CREB pathway') was associated with OVCA overall survival. The identification of the Transcription/CREB pathway (associated with OVCA cell line platinum sensitivity and overall survival) could improve patient stratification for treatment with current therapies and the rational selection of future OVCA therapy agents targeted to these pathways.

Signal Transduction

Humans

Carboplatin - administration & dosage

Treatment Outcome

Ovarian Neoplasms - mortality

Cisplatin - administration & dosage

Antineoplastic Combined Chemotherapy Protocols - therapeutic use

Cell Line, Tumor - immunology

Female

Ovarian Neoplasms - metabolism

Cyclic AMP Response Element-Binding Protein

Paclitaxel - administration & dosage

Ovarian Neoplasms - drug therapy

Details

Title: Subtitle: In vitro analysis of ovarian cancer response to cisplatin, carboplatin, and paclitaxel identifies common pathways that are also associated with overall patient survival
Creators: E Bicaku - Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
Y Xiong
D C Marchion
H S Chon
X B Stickles
N Chen
P L Judson
A Hakam
J Gonzalez-Bosquet
R M Wenham
S M Apte
W Fulp
C L Cubitt
D-T Chen
J M Lancaster
Resource Type: Journal article
Publication Details: British journal of cancer, Vol.106(12), pp.1967-1975
DOI: 10.1038/bjc.2012.207
PMID: 22596241
PMCID: PMC3388569
NLM abbreviation: Br J Cancer
ISSN: 0007-0920
eISSN: 1532-1827
Publisher: England
Grant note: R21 CA110499 / NCI NIH HHS R21 CA-110499-01A2 / NCI NIH HHS P30 CA076292 / NCI NIH HHS
Language: English
Date published: 06/05/2012
Academic Unit: Obstetrics and Gynecology
Record Identifier: 9983931810402771

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