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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

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)

Citation(s)

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)

Illumina HumanHT-12 V3.0 expression beadchip

Samples (23)

More...

GSM780707	Untreated after 4 days (C1_1)
GSM780708	Untreated after 4 days (C2_1)
GSM780709	Untreated after 4 days (C3_1)

Relations

BioProject

Download family	Format
SOFT formatted family file(s)	SOFT
MINiML formatted family file(s)	MINiML
Series Matrix File(s)	TXT

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
Processed data included within Sample table

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