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| Status |
Public on Aug 01, 2015 |
| Title |
Apoptosis enhancing drugs overcome innate platinum resistance in CA125 negative tumor initiating populations of high grade serous ovarian cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
High 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.
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| Overall design |
mRNA profiles of CA125 positive and negative populations, generated by next generation sequencing of populations FACS isolated from 10 independent dissociated primary human high grade serous ovarian cancers, were compared.
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| |
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| Contributor(s) |
Lu J, Janzen DM |
| Citation(s) |
26234182 |
| Submission date |
Jun 19, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Sanaz Memarzadeh |
| E-mail(s) |
smemarzadeh@mednet.ucla.edu
|
| Organization name |
UCLA
|
| Department |
Obstetrics and Gynecology
|
| Lab |
3017 TLSB
|
| Street address |
610 Charles E Young Dr East
|
| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA287643 |
| SRA |
SRP059732 |
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