We focus on identification of kinase signaling pathways, inhibition of which could be used in combination with endocrine therapy for treatment of Estrogen Receptor (ER)-positive breast cancer. The p90 Ribosomal S6 Kinase (RSK), an effector of the MAPK signaling pathway, plays a key role in cell growth and survival, through the regulation of many downstream targets, and may serve a role in promoting response to endocrine therapy. To further elucidate the role of RSK in crosstalk with estrogen signaling pathways, we first examined the expression of RSK in ER-positive breast cancer subtype and correlation with phosphopeptide abundance using phosphoproteomics analysis. Our results suggest that RSK is highly expressed in ER-positive breast cancer and also promotes the phosphorylation of many targets involved in cell growth and survival signaling pathways. Our ongoing investigation characterizes the role of new targets of RSK in ER-positive breast cancer, with the long-term goal to develop further targeted therapies that can increase sensitivity to endocrine therapy and prevent the development of therapeutic resistance.
