期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/ncomms8956
关键词
-
资金
- NIH/NCI [R01CA183877]
- American Cancer Society [VA CDA-2, RSG-14-217-01-TBG]
- NIH/National Center for Advancing Translational Science UCLA CTSI [UL1TR000124]
- Ovarian Cancer Circle Inspired by Robin Babbini
- Leath L. and Marcia L. Millen Family Fund
- Jonsson Cancer Center Foundation/UCLA
- Lynne Cohen Foundation
- Phase One Foundation
- Gynecologic Oncology Discovery Lab Foundation
- NATIONAL CANCER INSTITUTE [R01CA183877] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR000124] Funding Source: NIH RePORTER
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据