title: In vitro analysis of ovarian cancer response to cisplatin, carboplatin, and paclitaxel identifies common pathways that are also associated with overall patient survival.
abstract: 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, 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: E
authors.initials: E
authors.lastname: Bicaku
authors.forename: Y
authors.initials: Y
authors.lastname: Xiong
authors.forename: D C
authors.initials: DC
authors.lastname: Marchion
authors.forename: H S
authors.initials: HS
authors.lastname: Chon
authors.forename: X B
authors.initials: XB
authors.lastname: Stickles
authors.forename: N
authors.initials: N
authors.lastname: Chen
authors.forename: P L
authors.initials: PL
authors.lastname: Judson
authors.forename: A
authors.initials: A
authors.lastname: Hakam
authors.forename: J
authors.initials: J
authors.lastname: Gonzalez-Bosquet
authors.forename: R M
authors.initials: RM
authors.lastname: Wenham
authors.forename: S M
authors.initials: SM
authors.lastname: Apte
authors.forename: W
authors.initials: W
authors.lastname: Fulp
authors.forename: C L
authors.initials: CL
authors.lastname: Cubitt
authors.forename: D-T
authors.initials: DT
authors.lastname: Chen
authors.forename: J M
authors.initials: JM
authors.lastname: Lancaster
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D045744:Cell Line, Tumor / Q000276:immunology; D002945:Cisplatin / Q000008:administration & dosage; D017362:Cyclic AMP Response Element-Binding Protein; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D017239:Paclitaxel / Q000008:administration & dosage; D015398:Signal Transduction; D016896:Treatment Outcome
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin