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Target activation predicts therapeutic benefit

Final Activity Report Summary - PREDICTIVE DIAGNOSIS (Target activation predicts therapeutic benefit)

This project was originally designed prior to Professor John Bartlett, who is the project coordinator, moving his laboratory to the University of Edinburgh in March 2006. This move necessitated a short delay in the recruitment of the first researcher, Hans-Christian Pedersen, who moved to Edinburgh to commence work on the project in June 2006. A second delay was caused by the withdrawal from the project of the candidate from Glasgow and Dr Vilius Pigaga was appointed to the post on 1 November 2006 and seconded to Dako under the terms of the project.

These changes were identified in the year 1 report. In 2006, Dako underwent significant re-structuring. This meant protracted discussions relating to the partnership agreement which has now been successfully completed. In 2007 / 2008, the period under report, Dako underwent further restructuring leading to the departure of Kurt Pii, the senior scientist at Dako responsible for the project. Dr Henrik Winter and Dr Sussie Steen have assumed responsibility for this project at Dako. These challenges have had a number of effects on the detail of the project, without affecting the overall strategic objective of testing and validation of proteomic markers for detection of activated proteins in cancer diagnostics.

In 2008 / 2009 the two fellows Hans Christian Pedersen and Vilius Pigaga returned to their 'host' institutions and this report focuses largely on the achievements during this period. Due to delays in recruitment noted above the final period of the grant will actually terminate in November 2009, several months after the scheduled termination dates.

Over the period of the project, there was a necessary delay, on behalf of Dako, to the delivery of milestones due to delay in recruitment. There have been agreed changes to the specific proteins to be targeted which have taken place during the regular teleconferences and face to face meetings held during the project to date.

The objective of the program was the development and utilisation of novel IHC reagents that recognise three specific proteins and significant targets within the receptor Tyrosine Kinase/ PI3k/ Akt/ mTor pathway. Overexpression or inhibition of these pathways causes aberrant cellular processes that can lead to pathogenesis and cancer. In addition, these pathways have been associated with drug resistance in cancer. The expression and activation level of these proteins may provide new disease indication of relevance in clinical research and may be of key interest as an essential tool in diagnostic, prognostic or predictive patient profiling for therapy.

Six poster presentations: national (United Kingdom National Cancer Research Network), Cancer Research Centre symposium (2007), international (United States cell signalling meeting, January 2007), EBCC6 (Germany, breast cancer conference), SABCS 2008; 2009 (United States breast cancer conference) have resulted from the TOK to date. In addition, one oral presentation at EBCC6 and one book chapter on predictive markers in targeted treatment of cancer resulted from TOK. Results will be further disseminated via peer reviewed publications and presentations during 2010.

Two papers have recently been published from the results of Hans Christians stay in Edinburgh, additional papers are under review.