The posttranslational changes of components involved in the signal transduction cascades, typically initiated by the binding of a ligand to its receptor, are strong indicators of the destiny of the cell in which it takes place. Defects in cell signalling play a central role in cancer cell growth, survival, invasion and metastasis.
Whereas the expression levels of important receptors, such as the estrogen receptor (ER) and the herceptin receptor (HER-2), are well established in cancer diagnostics and for selection of patients for targeted therapy, recent studies, for example of the epidermal growth factor receptor (EGFR, HER-1), have shown that receptor expression levels may often be insufficient as biomarkers in cancer. In an extended collaboration between University of Oxford and the Danish diagnostics company, DakoCytomation, the present project will lead to the development of immunoassays for activated forms of signal transduction components downstream to receptors of the HER-family and for nuclear proteins.
In particular, immunohistochemical assays for phosphorylated kinases will be developed and clinically characterized on tumour tissues, but also other potential biomarkers, such acetylated and otherwise modified nuclear proteins will be evaluated, and other assays, such as immunocytochemistry, flow cytometry, and ELISA are included and supplemented by in-situ hybridisation. The resulting pharmacodiagnostic applications will most likely be narrow panels of biomarkers in arrays rather than individual antigens.
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