Abstract 4799: Identification of drug resistance targets in ovarian cancer using a proteomic approach

Abstract

Abstract Ovarian cancer ranks first in the number of deaths and second in the number of new cases among gynecological cancers. In the majority of the cases, surgery is the intervention of choice, but chemotherapy has progressed considerably over the last years. First-line treatment for advanced-stage disease is a combination of carboplatin and paclitaxel. However, drug resistance has become a major obstacle to the successful chemotherapeutic treatment of human cancers. Currently, there is no clear consensus on treatment options for ovarian cancer patients who acquired drug resistance, due to the lack of knowledge about drug resistance mechanisms. There is an urgent need to explain how drug resistance occurs and to identify proteins related to this phenomenon, so that inhibitors can be designed. The aims of this study are to develop and optimise a two-dimensional gel electrophoresis method to compare protein profile of human ovarian cancer cell lines, which are sensitive or resistant to anticancer chemotherapy, so that proteins related to drug resistance can be identified using mass spectrometry. The parental ovarian cancer cell line models PEO1 and SKOV-3 are used as drug sensitive reference cell lines. Novel drug resistant models, derived from the parental lines, with in vitro acquired resistance to paclitaxel and carboplatin are used alongside their respective drug sensitive parental counterparts. Proteins related to tumorigenesis or drug resistance, either new or previously reported, were identified in at least one of the three cell lines. These proteins belong to different classes and are responsible for distinct functions within the cell, such as cytoskeleton and cell structure, detoxification and stress response, and cellular metabolism. This is the first proteomic study on these specific ovarian cancer cell lines using paclitaxel and carboplatin. The results obtained will be useful for further studies of resistance mechanisms and screening of resistance biomarkers for the development of tailored therapeutic strategies. 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 4799. doi:1538-7445.AM2012-4799