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

被引：33

作者：

Bicaku, E. ^{[1
,2
]}

Xiong, Y. ^{[1
,2
]}

Marchion, D. C. ^{[1
,2
]}

Chon, H. S. ^{[1
]}

Stickles, X. B. ^{[1
]}

Chen, N. ^{[1
]}

Judson, P. L. ^{[1
,3
]}

Hakam, A. ^{[3
,4
]}

Gonzalez-Bosquet, J. ^{[1
,3
]}

Wenham, R. M. ^{[1
,2
,3
]}

Apte, S. M. ^{[1
,3
]}

Fulp, W.

Cubitt, C. L.

Chen, D-T

Lancaster, J. M. ^{[1
,2
,3
]}

机构：

[1] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Womens Oncol, Tampa, FL 33612 USA

[2] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Expt Therapeut Program, Tampa, FL 33612 USA

[3] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Oncol Sci, Tampa, FL 33612 USA

[4] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Anat Pathol, Tampa, FL 33612 USA

来源：

BRITISH JOURNAL OF CANCER | 2012年 / 106卷 / 12期

关键词：

ovarian cancer; platinum agents; taxane; chemo-response; gene expression; CELL-DEATH; BINDING PROTEIN; BH3; DOMAIN; STAGE-III; PHASE-III; BAD; PHOSPHORYLATION; APOPTOSIS; BCL-2; CYCLE;

D O I：

10.1038/bjc.2012.207

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BACKGROUND: 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. METHODS: Ovarian cancer cell lines (n = 36) were treated with carboplatin, cisplatin, paclitaxel, or carboplatin-paclitaxel (CPTX). For each cell line, IC50 levels were quantified and pre-treatment gene expression analyses were performed. Genes demonstrating expression/IC50 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. RESULTS: 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. CONCLUSION: 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. British Journal of Cancer (2012) 106, 1967-1975. doi:10.1038/bjc.2012.207 www.bjcancer.com Published online 17 May 2012 (C) 2012 Cancer Research UK

引用

页码：1967 / 1975

页数：9

共 64 条

[41] Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: A Gynecologic Oncology Group study [J].