Unknown

Dataset Information

0

An apoptosis-enhancing drug overcomes platinum resistance in a tumour-initiating subpopulation of ovarian cancer.


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.

SUBMITTER: Janzen DM 

PROVIDER: S-EPMC4532886 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

An apoptosis-enhancing drug overcomes platinum resistance in a tumour-initiating subpopulation of ovarian cancer.

Janzen D M DM   Tiourin E E   Salehi J A JA   Paik D Y DY   Lu J J   Pellegrini M M   Memarzadeh S S  

Nature communications 20150803


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 birin  ...[more]

Similar Datasets

2015-08-01 | E-GEOD-70072 | biostudies-arrayexpress
2015-08-01 | GSE70072 | GEO
| S-EPMC7381609 | biostudies-literature
| S-EPMC6935502 | biostudies-literature
| S-EPMC10956367 | biostudies-literature
| S-EPMC2363292 | biostudies-other
| S-EPMC4453841 | biostudies-literature
| S-EPMC3217125 | biostudies-literature
| S-EPMC4147310 | biostudies-literature
| S-EPMC9276031 | biostudies-literature