Title: Novel Approaches to Increase Ovarian Tumor Cell Response to Cisplatin
Authors: Marissa R. Anderson1,2, Joshua Roxby1, Brenee King1, Ellen Hatch1, Eric Carnes2 and Laurie G. Hudson1
Affiliations: 1Department of Pharmaceutical Sciences, University of New Mexico 2Department of Chemical and Nuclear Engineering, University of New Mexico
Abstract: It is estimated that 22,280 women will be diagnosed with ovarian cancer in the United States in 2012. Current therapies include treatment with a platinium-based chemotherapeutic, often in combination with a taxane. There is an urgent need for improved chemotherapeutic strategies and successful tumor targeting for ovarian cancer treatment. We have conducted studies to investigate an alternative strategy to inhibit DNA repair and the activity of the DNA repair protein poly(ADP-ribose) polymerase (PARP). The novel drug combination of cisplatin and arsenic trioxide (ATO) is proposed to enhance cytotoxicity by increasing cisplatin-mediated DNA damage. Both cisplatin and ATO cause concentration-dependent cytotoxicity of ovarian tumor cells, but the combination of both drugs exceeds the action of either agent alone. Preliminary studies suggest that ATO inhibits PARP activity and increases DNA damage caused by cisplatin. The next phase of the project will involve analysis of an innovation drug delivery method that uses peptide targeted protocells to target tumor cells. The long term goal of the project is to identify new approaches to improve ovarian cancer treatment.