Abstract 1060: Integrated target discovery in the EMPathy Breast Cancer Network - Multidimensional analysis of epithelial mesenchymal plasticity (EMP) in experimental systems

Abstract

Abstract The ability of breast cancer cells to switch between epithelial and mesenchymal phenotypes may be key to their survival in new environments, resistance to therapies and ability to form metastases. Epithelial mesenchymal plasticity (EMP) is instrumental in embryological development and has been implicated in stemness, therapy resistance and metastasis of breast cancer. EMP markers are enriched in basal-like, triple negative breast cancer, which is a type of breast cancer associated with early recurrence and poor prognosis, and established as a common phenotype in women with BRCA1 mutations. The EMPathy Breast Cancer Network (BCN) is a national collaborative effort including scientists, surgeons, medical oncologists and a consumer advocate investigating the role of EMP in breast cancer recurrence. The 7 thematic research projects of EMPathy BCN, including the 9 program-funded ‘Satellite’ projects, are aligned with the Cooperative Research Centre for Cancer Therapeutics (CTx) (www.cancercrc.com/index), so that any potential drug targets identified may progress into the CTx drug development program. Multiple parallel approaches in the Target Discovery theme were used to identify candidate regulators and effectors of EMP. A total of 10 functional or gene expression experiments provided 7,950 significant events in any one system, which were cross referenced against 10 public breast cancer datasets relevant to EMP and/or breast cancer stem cells. A series of criteria were used to select a panel of 127 candidates that were combined with 123 ad hoc candidates (mainly hits close to the cut-off and breast cancer context genes) to give a total of 250 candidates to be analysed in breast cancer tissues using Nanostring technology. The 2,301 ‘significant events’ in any functional screen were further cross-referenced to 10 public functional datasets relevant to EMP in any system and a series of criteria were used to select a panel of 320 candidates that are to be analysed in an siRNA ‘functional screen' of multiple breast cancer cell lines, to support the choice of Candidate Targets for drug development. Ongoing studies will address the biology behind selected Candidates. This work and the EMPathy BCN is supported by a NBCF National Collaborative Research Program Grant. Citation Format: Tony Blick, Gayle Phillip, Eva Tomaskovic-Crook, Annet Hammacher, Nicholas Wong, Izhak Haviv, The EMPathy Breast Cancer Network, Greg Goodall, Melissa Davis, Erik W. Thompson. Integrated target discovery in the EMPathy Breast Cancer Network - Multidimensional analysis of epithelial mesenchymal plasticity (EMP) in experimental systems. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1060. doi:10.1158/1538-7445.AM2014-1060