title: Role of phosphoproteomics in the development of personalized cancer therapies.
abstract: Cell signalling pathways driven by protein and lipid kinases contribute to the onset and progression of virtually all cancer types. Consequently, several inhibitors against these enzymes have clinical utility for the treatment of different forms of cancer. A problem that hampers further development is that not all patients respond equally well to kinase inhibitors and a significant proportion of those that initially respond eventually develop resistance. This review considers how an integrative analysis of kinase signalling may be used to address this issue. Advances in the biophysics of mass spectrometry, in biochemical procedures for phosphopeptide enrichment, and in computational approaches for label-free quantification have contributed to the development of phosphoproteomics workflows compatible with the analysis of clinical material. These developments, together with new bioinformatics tools to derive information on signalling circuitry from phosphoproteomics data, allow investigating kinase networks with unprecedented depth. Phosphoproteomics technology is starting to be used in translational research and, with further developments, such methods may also be able to measure the circuitry of cancer signalling networks in routine clinical assays. This review reflects on how this information could be used to accurately predict the best kinase inhibitor for each individual cancer patient.
authors.affiliation: Integrative Cell Signalling and Proteomics, Centre for Haemato-Oncology, John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, UK.
authors.forename: Pedro R
authors.initials: PR
authors.lastname: Cutillas
mesh_terms: D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D009369:Neoplasms / Q000378:metabolism*; D010748:Phosphopeptides / Q000032:analysis; D010750:Phosphoproteins / Q000032:analysis; D057285:Precision Medicine / Q000379:methods; D040901:Proteomics / Q000379:methods; D049490:Systems Biology / Q000379:methods*
chemical_list: D010748:Phosphopeptides; D010750:Phosphoproteins
keywords: Mass spectrometry; Network biology; Precision medicine; Systems biology