Abstract

Reverse Phase Protein Arrays as a Tool to Identify New Biomarkers and Potential Therapeutic Targets for Breast Cancer Subtypes

Leanne De-Koning, Manager, Institut Curie

Invasive lobular carcinomas (ILC) and triple negative breast cancers (TN) are two types of breast cancer that are associated with bad prognosis and for which no targeted therapies are available. It is now clear that the success and the failures of targeted therapies are related to the activation status of cell signalling pathways in the tumor. We therefore argued that, in order to find new potential therapeutic targets in these two groups of breast cancer, we need to map activated signalling pathways and identify driver proteins. We used reverse phase protein arrays (RPPA) to screen hundreds of ILCs and TN breast cancers collected from different European comprehensive cancer centers. RPPA is a high–throughput dot-blot technology which uses very little biological material. We particularly focused on receptors, kinases and their substrates. Integration of RPPA data with clinical data and other sources of molecular profiling data, such as NGS, RNAseq and transcriptome data, allows us to identify new subgroups of patients that are of clinical relevance, new predictive biomarkers for both diagnostic and prognostic purposes and new potential therapeutic targets. These are then further validated by immunohistochemistry and on cultured cell lines.  We thus hope to provide new tools for a better treatment of patients suffering from these two types of breast cancer.