EACR Special Session at ECCO-14

Dysregulated cellular signalling networks underlie the development or progression of multiple human pathologies, including autoimmune diseases, metabolic disorders, and cancer. To develop optimal therapeutics to treat these disease states, it is necessary to define not only which components are dysregulated, but also how this lack of regulation affects the biology of the system. In the past, identification of dysregulated components in the signalling network has been performed on a relatively small scale, interrogating the activity or phosphorylation status of selected proteins, and testing their contribution to the biological phenotype. These studies have uncovered much of the existing knowledge of cellular signalling and have identified many of the existing drug targets. However, this approach to signalling networks is ultimately limited, as it does not yield systems-level information, including cross-talk and feedback between multiple components and pathways. In fact, to understand complex biological processes such as the development of resistance to therapeutic agents, it may be necessary to capture a larger-scale view of the network to identify which compensation mechanisms for inhibition of the targeted nodes. To generate this systems-level view of cellular signalling networks, my lab has developed a mass spectrometrybased technology enabling quantification of hundreds of tyrosine phosphorylation sites across multiple biological samples, all in a single analysis (1).