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Series GSE31432 Query DataSets for GSE31432
Status Public on May 03, 2012
Title Defining the molecular response to trastuzumab, pertuzumab and combination therapy in ovarian cancer
Organism Homo sapiens
Experiment type Expression profiling by array
Summary The purpose of this study was to characterise the effects of trastuzumab and pertuzumab, either as single agents or as combination therapy on gene and protein expression in human ovarian cancer in vivo. Illumina BeadChips were used to profile the transcriptome after four days treatment of SKOV3 tumor xenografts. Although genes involved with HER2, MAP-kinase and p53 signaling pathways were commonly induced by all treatments, a greater number and variety of genes were differentially expressed by the complementary combination therapies compared to either drug on its own. The protein level of the CDK-inhibitors p21 and p27 were increased in response to both agents alone and further by the combination; pERK signaling was inhibited by all treatments; but only pertuzumab alone inhibited pAkt signaling. The expression of proliferation, apoptosis, cell division and cell cycle markers was distinct in a panel of primary ovarian cancer xenografts, suggesting heterogeneity of response in ovarian cancer and the need to establish biomarkers of response.
This first comprehensive study of the molecular response to trastuzumab, pertuzumab and combination therapy in vivo highlights that there are both common and distinct downstream effects to different HER2 antibodies and that pathways may be invoked more strongly or in a different manner by a combination of agents. Some of the in vivo results for ovarian tumors differ from previous in vitro studies in breast cancer cells, emphasizing that the molecular response to anti-cancer agents involves variable and complex disease-specific interactions of signaling mechanisms.
 
Overall design SCOV3 Ovarian cell line xenografts treated with Trastuzumab, pertuzumab or combination after 4 days
 
Contributor(s) Sims AH
Citation(s) 22549178
Submission date Aug 17, 2011
Last update date Aug 16, 2018
Contact name Andrew H Sims
E-mail(s) andrew.sims@ed.ac.uk
Organization name University of Edinburgh
Department Institute of Genetics and Molecular Medicine
Lab Applied Bioinformatics of Cancer
Street address Systems Medicine Building
City Carrington Crescent
State/province Edinburgh
ZIP/Postal code EH4 2XR
Country United Kingdom
 
Platforms (1)
GPL6947 Illumina HumanHT-12 V3.0 expression beadchip
Samples (23)
GSM780707 Untreated after 4 days (C1_1)
GSM780708 Untreated after 4 days (C2_1)
GSM780709 Untreated after 4 days (C3_1)
Relations
BioProject PRJNA145793

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE31432_RAW.tar 6.2 Mb (http)(custom) TAR
GSE31432_non-normalized_data.txt.gz 7.2 Mb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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