We verified that the SEOC GDA models respond to cisplatin or olaparib similarly to patients. olaparib is efficacious only for BRCA deficient tumors and cisplatin is optimally effective in these tumors. The combination of these two drugs for BRCA deficient tumors is no more efficacious than cisplatin alone. We have evaluated consolidated therapy for BRCA1-deficient GDA tumors in which mice are treated with cisplatin to debulk tumors followed by treatment with an FDA-approved drug shown in drug library screens to be effective at killing both human and mouse SEOC derived cells in 2-D culture. With standard routes of introduction, the compound was not more effective than the vehicle control. We are now evaluating the efficacy of this drug when delivered by implanted continuous dosing pumps. Studies for all other objectives are currently in progress.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011353-06
Application #
9153877
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
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Szabova, Ludmila; Yin, Chaoying; Bupp, Sujata et al. (2012) Perturbation of Rb, p53, and Brca1 or Brca2 cooperate in inducing metastatic serous epithelial ovarian cancer. Cancer Res 72:4141-53
Serber, Daniel W; Rogala, Allison; Makarem, Maisam et al. (2012) The BRG1 chromatin remodeler protects against ovarian cysts, uterine tumors, and mammary tumors in a lineage-specific manner. PLoS One 7:e31346
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