Role of PI3Ks in cancer, diabetes and inflammation
Members of the 'Characterisation of signalling and physiologic roles of the class II PI 3-kinases' (PI3KC2) project developed and refined mass spectrometry-based techniques for label-free phosphoproteomics that will identify PI3K proteins involved in cancer and provide targets for therapy. This phosphoproteomics approach enables rapid detection and quantification of several protein phosphorylation sites (indicative of kinase activity) to elucidate kinase signalling in tissues. Pescal, a computer programme, was successfully modified to improve the accuracy of mass spectrometry data analysis that was later used by other Marie Curie projects. Phosphoproteomics of mice-derived leukaemia cells identified key PI3K phosphorylation sites. Analysis revealed that cancer cell resistance to kinase-inhibitor drugs depends on both the activity of the targeted pathway and parallel kinase pathways. Twenty cases of primary leukaemias were profiled and specific PI3K phosphorylation sites were discovered that could help in predicting the efficacy of cancer therapy. The label-free mass spectrometry-based phosphoproteomics technique has subsequently been licensed to a company that provides phosphoproteomics services to biotechnology and pharmaceutical client companies. PI3KC2 project outcomes have laid the foundation for developing personalised cancer treatment. Techniques developed by this project will benefit other Marie Curie projects and also the EU biotechnology sector.
