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.
Szabova, Ludmila; Bupp, Sujata; Kamal, Muhaymin et al. (2014) Pathway-specific engineered mouse allograft models functionally recapitulate human serous epithelial ovarian cancer. PLoS One 9:e95649 |
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 |
Walrath, Jessica C; Hawes, Jessica J; Van Dyke, Terry et al. (2010) Genetically engineered mouse models in cancer research. Adv Cancer Res 106:113-64 |