Analysis Of Biological Pathways Associated With Epirubicin And/Or Cyclophosphamide Response By Pathway Enrichment Analysis In Human Breast Cancers

Recently, a number of different approaches for improving cancer treatment have been developed. One scientific approach is to understand the biochemical pathways and coding genes involved in cancer causation, while other approaches look to distinguish the biochemical pathways involved in drug response. Many chemotherapeutic drugs have been developed targeting different cellular properties, and even more targeted therapies impacting specific oncogenic pathways are on the horizon. Pathways implicated in drug response have been studied to determine why some tumors might respond to a given chemotherapy while others do not. Understanding these pathways may provide potential for improving therapeutic efficacy. Pathway analysis methods have been proposed to discover pathways of interests using gene expression profiling. In this study, the biological pathways associated with response to Epirubicin (E), Cyclophosphamide (C) or the combination of the two drugs (combo EC) were evaluated in both breast cancer cell lines and patients. Thirty immortalized breast cancer cell lines were evaluated for response to these drugs using ChemoFx®. Area under the dose-response curve (AUC) was calculated to measure the chemosensitivity. We applied pathway enrichment to detect specific biochemical pathways associated with these drugs based on biological pathway databases (Kyoto Encyclopedia of Genes and Biocarta), breast cancer cell lines’ drug responses and public microarray data. Comparison of pathways associated with single drug E, C, and combo EC revealed that there are pathways associated with drug combination but not significantly associated with single drugs. These drug response-associated pathways offer great potential for new biomarker identification and drug targeting discovery. In addition, EC associated pathways in breast cancer patients were identified using public microarray data and the associated patient clinical outcomes. Of importance, four biological pathways related to adherens junction, leukocyte transendothelial migration, regulation of actin cytoskeleton and ribosomal protein were identified as EC response-associated pathways in both breast cancer cell lines and patients. These common EC response-associated pathways indicate the potential possibility to use cell line in vitro drug responses to predict patient chemotherapy outcomes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 118.