Abstract 815: The role of spleen tyrosine kinase (SYK) in paclitaxel resistant ovarian cancer

Abstract

Abstract The development of resistance to paclitaxel represents a general challenge in clinical oncology, particularly in ovarian serous carcinomas (OSCs), the most common and lethal form of ovarian cancer. Initial treatment with a taxane and platinum combination regimen is standard and while the majority of women will achieve a major response to this treatment, the mortality of ovarian cancer is directly related to the tumor's development of chemoresistance. Using a proteomic approach to comprehensively compare the protein expression profiles of primary and recurrent OSC clinical samples, our laboratory previously identified several novel candidate proteins associated with the development of recurrent OSC. In this study, we focus on evaluating one of these proteins, spleen tyrosine kinase (SYK), a non-receptor tyrosine kinase, and its role in the maintenance of paclitaxel resistance in OSC. We have determined that increased expression of SYK in OSC tumor cells obtained from ascites and/or pleural effusion fluid is associated with a poorer response to chemotherapy. Using a cell culture system, we found that two OSC cell lines show an increased expression of SYK after development of in vitro resistance to paclitaxel treatment. More importantly, we demonstrate that SYK small compound inhibitors significantly resensitize the tumor cells to paclitaxel. Our results suggest that SYK plays a role in maintaining paclitaxel resistance in OSC. Recently an oral SYK inhibitor was found to be safe and effective in treating rheumatoid arthritis and non-Hodgkin lymphoma; our results suggest a potential translational use for this inhibitor as a chemosensitizing agent in patients with OSC. 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 815. doi:1538-7445.AM2012-815