Abstract 380: Optimization of novel therapeutic paradigms for ovarian cancer using molecular imaging

Abstract

Abstract Ovarian cancer is the fifth leading cause of cancer death among American woman. Platinum-based chemotherapy, such as cisplatin, represents the standard of care for ovarian cancer. However, toxicicity and acquired resistance to cisplatin have been proven challenging in the treatment of cancer patients. Here, we evaluate the efficacy of targeted inhibition of Akt in combination with cisplatin in an ovarian endometrioid adenocarcinoma (OEA) mouse model wherein Wnt and PI3K signaling pathways are disrupted thus recapitulating the human disease. In cell culture and mouse xenograft models, inhibition of Akt activity in combination with cisplatin is more potent at inducing apoptosis compared to either agent alone. To further explore this finding in living animals, we incorporate a bioluminescence apoptosis reporter into the existing OEA mouse model, to enable monitoring of apoptosis dynamically and non-invasively in real time. Our results demonstrate that Akt inhibitors augment the efficacy of cisplatin by inducing apoptosis more efficiently in our newly developed transgenic OEA model. Magnetic resonance (MR) imaging was also accomplished to determine tumor burden and normalize changes in bioluminescence. Our results show that inhibition of Akt sensitizes OEA to apoptosis in response to cisplatin thus resulting in reducing tumor burden. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 380. doi:1538-7445.AM2012-380