TRANSDUCTION MARKERS · Novel biomarkers for targeted therapy in cancer: Signal transduction components post-translationally modified in response to receptor activation
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2005-07-01 → 2009-06-30
- EU contribution
- €357,093
- Participants
- 2
- Scheme
- TOK
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Results in brief
Final Activity Report Summary - TRANSDUCTION MARKERS (Novel biomarkers for targeted therapy in cancer: Signal transduction components post-translationally modified in response to receptor activation)
Many cancers could be identified by using antibodies to indicate the presence of certain proteins within human cancer cells. Detection of these proteins using antibodies allowed for the identification of a cancer type, a determination of how dangerous the cancer was and, also, for a determination of whether the cancer might be successfully treated with certain anti-cancer medicines. This project aimed to make and test new antibodies that could be used to determine how dangerous a patients cancer would be as well as to give the patient's doctor an idea of what medicines would be suitable to treat the patient's cancer. More specifically, this project set out to make antibodies that were of unrivalled quality so that the patient's doctor could have complete faith in the results obtained using the antibody. Making high quality antibodies was technically very difficult and several antibodies already existed on the global market. Unfortunately, these antibodies often detected other proteins as well as their target protein giving confusing or incorrect results. Many new antibodies were made during the course of this project but two were shown to be of a suitably high quality for use in hospitals. These two antibodies were perfectly specific for their own particular proteins in cancer cells, and tests to determine their performance in a hospital setting showed good results. Working in collaboration with real hospitals in Oxford and Budapest our antibodies were shown to provide a reliable and accurate diagnosis allowing doctors to make fast and accurate decisions regarding patient treatment; thus improving the welfare of the patient. As the design and making of these antibodies was technically difficult we also investigated new and improved ways of making and testing new antibodies. New tests were developed using actual cancer cells grown artificially in the laboratory and these tests proved to be very successful at selecting new high quality antibodies. Using laboratory grown cancer cells to select antibodies that were then capable of detecting human cancer cells proved to significantly improve both the speed and accuracy of antibody preparation. We also improved the current antibody making strategies by integrating the latest scientific research technology into the present antibody preparation methods. This allowed us to shorten the time taken to make new antibodies and to increase our level of knowledge about the quality of the antibody when used in a hospital setting. It was anticipated that when these antibodies would have become widely available they would provide doctors with new tools to improve patient treatment by allowing for the fast and correct administration of effective medicines to cancer patients. Dako Denmark launched four antibody products in 2007 and 2008, which were developed as part of this project, helping pathologists and researchers all over the world.
Data: CORDIS, © European Union
Project objective
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.
Original text from CORDIS.
Participants
- DAKOCYTOMATION DENMARK A/S · GLOSTRUPCoordinatorCity levelDenmark
- CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD · OXFORDCity levelUnited Kingdom
Links
Data: CORDIS, © European Union
