Apoptosis enhancing drugs overcome innate platinum resistance in CA125 negative tumor initiating populations of high grade serous ovarian cancer
Transcriptomics Dataset
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General Information
AccessionGSE70072
TitleApoptosis enhancing drugs overcome innate platinum resistance in CA125 negative tumor initiating populations of high grade serous ovarian cancer
DescriptionHigh grade serous ovarian cancers (HGSC) are deadly malignancies that relapse despite carboplatin chemotherapy. Here we show that 16 independent primary HGSCs contain a CA125 negative population enriched for carboplatin resistant cancer initiating cells. Transcriptome analysis reveals up-regulation of homologous recombination DNA repair and anti-apoptotic signals in this population. While treatment with carboplatin enriches for CA125 negative cells, co-treatment with carboplatin and birinapant eliminates these cells in HGSCs expressing high levels of the inhibitor of apoptosis protein cIAP in the CA125 negative population. Birinapant sensitizes CA125 negative cells to carboplatin by mediating degradation of cIAP causing cleavage of caspase-8 and restoration of apoptosis. This co-therapy significantly improved disease free survival in vivo compared to either therapy alone in tumor-bearing mice. These findings suggest that therapeutic strategies that target CA125 negative cells may be useful in the treatment of HGSC.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE70072
RepositoryGene Expression Omnibus
Tools used to analyze the dataset

Dataset Accession

ARCHS4
Published September 2017
ARCHS4 provides access to gene counts from HiSeq 2000 and HiSeq 2500 platforms for human and mouse experiments from GEO ...
4645
Clustergrammer
Published October 2017
Web-based tool for visualizing and analyzing high-dimensional data as interactive and shareable heatmaps
4645
Canned Analyses generated with the dataset

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Interactive heatmap visualization of RNA-seq dataset GSE70072
Highly interactive web-based heatmap visualization of the top 500 most variable genes in t...
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