Abstract 4027: Pathway analysis of chemoresistance in ovarian cancer cell lines.

Abstract

Abstract Introduction: Ovarian Cancer is the most deadly female reproductive cancer and fifth most common cause of death from cancer among women. Limited characterization of the chemoresistant population demonstrates the need for improved therapy for ovarian cancer. Pathway analysis of microarray data of paired chemosensitive and chemoresistant ovarian cancer cell lines may help to elucidate important contributors to chemoresistance, and paired analyses can eliminate the significant heterogeneity among patient samples. Significant genes may serve as potential targets for novel drug therapies. Some genes likely contribute to resistance of multiple chemotherapies and represent common pathways of resistance. Methods: Microarray data of three pairs of chemosensitive and chemoresistant ovarian cancer cell lines were analyzed using GeneSpring Single Experiment Analysis of 517 pathways. These pairs include SKOV3ip1 and SKOV3TRip2 (taxane-resistant), HeyA8 and HeyA8MDR (multi-drug resistant), and A2780cp20 and A780cp55 (increasing cisplatin resistance). Significant genes within significant pathways were compared between types of drug resistance. Results: Between SKOV3ip1 and SKOV3TRip2, 8 pathways were significantly (p<0.001) modulated, dominated by the selenium pathway and folate/B12 metabolism. Between HeyA8 and HeyA8MDR, 9 pathways were significantly modified, led by DNA regulation and cell cycle progression. These differences between the SKOV3 model were interesting, given that both chemoresistant lines were developed in the same way. In A2780cp20 and A2780cp55, 7 pathways were significantly affected, highlighted by members of the Electron Transport Chain and controls on oxidative phosphorylation and autophagy. Validation of individual genes as important to chemoresistance will follow from this analysis. Conclusions: Multiple pathways are implicated in chemoresistance, even when selected by the same chemotherapeutic agent. Pathways contributing to metabolism, DNA repair, cell cycle control, and stress responses dominated. The high variability in pathway overexpression highlights the importance of patient-specific approaches to overcoming chemoresistance in ovarian cancer. Citation Format: William P. Jackson, Ashwini A. Katre, Zachary A. Dobbin, Adam D. Steg, Charles N. Landen. Pathway analysis of chemoresistance in ovarian cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4027. doi:10.1158/1538-7445.AM2013-4027