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- W1781170077 abstract "High-grade serous ovarian cancers (HGSCs) are deadly malignancies that relapse despite carboplatin chemotherapy. Here we show that 16 independent primary HGSC samples contain a CA125-negative population enriched for carboplatin-resistant cancer initiating cells. Transcriptome analysis reveals upregulation 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 improves disease-free survival in vivo compared with either therapy alone in tumour-bearing mice. These findings suggest that therapeutic strategies that target CA125-negative cells may be useful in the treatment of HGSC." @default.
- W1781170077 created "2016-06-24" @default.
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- W1781170077 date "2015-08-03" @default.
- W1781170077 modified "2023-10-01" @default.
- W1781170077 title "RETRACTED ARTICLE: An apoptosis-enhancing drug overcomes platinum resistance in a tumour-initiating subpopulation of ovarian cancer" @default.
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- W1781170077 doi "https://doi.org/10.1038/ncomms8956" @default.
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