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DISMAL: Molecular signatures as diagnostic and therapeutic targets for disseminated epithelial malignancies
- Abstract
- Disseminated tumour cells (DTC) occur at very low numbers and can be detected using sensitive immunostaining and PCR methods. However, sensitivity and in particular specificity of this approach need to be improved. Combining the expertise of 11 academic partners with long-term expertise in mi-crometastasis research the DISMAL-project will establish an improved platform for DTC detection with an increased sensitivity and in particular with a largely improved specificity. Besides DTC detection also analysis of circulating tumour DNA and RNA, and expression profiling of tumours are being ex-plored for assessment of minimal disease. We will focus on epithelial tumours as the most common types of solid tumours in the EU, investigating the carcinoma types that display different modes of metastatic spread. Dissemination via the blood circulation will be analyzed, using bone marrow as an important indicator organ to which epithelial tumour cells home. Using genomics-based approaches, novel diagnos-tic target molecules will be identified and validated in functional models. We will complement immuno-cytochemical DTC detection by additional genotypic and phenotypic markers relevant for metastatic progression. To further increase diagnostic precision we will analyze whether this improved platform can be combined with analysis of tumour characteristics that were revealed by the microarray analysis, and with evaluation of circulating tumour-associated DNA or RNA. Besides the primary focus on improve-ment of DTC-based diagnostic platforms, it is important to realize that these cells are the target cells for adjuvant chemotherapy and radiotherapy. In innovative DTC models, the efficacy of DTC treatment will therefore be analyzed and potential improvements studied. The translation of scientific knowledge into commercial products will be ensured by 3 SMEs with unique technological capabilities.
- Local Subprojectlead:
- Speicher Michael
- Duration:
- 01.02.2006-30.04.2009
- Programme:
- EU (FP-6)
- Subprogramme
- Biowissenschaften
- EU-Project Instruments
- Spec. Target. o Inn. Project (STREP)
- Type of Research
- applied research
- Staff
- Speicher, Michael, Project Leader
- MUG Research Units
- Diagnostic and Research Institute of Human Genetics
- Project partners
-
Agendia, Netherlands
Contact person: Dr. Bernhard Sixt; -
Applied Imaging, United Kingdom
Contact person: Dr. Paddy O'Kelly; -
Dept.Otolaryngology/Head-Neck Surgery/VU University Medical Center Amsterdam, Netherlands
Contact person: Prof. Ruud Brakenhoff; -
German Cancer Research Center, Germany
Contact person: Prof. Roland Eils; -
Heinrich Pette Institute, Germany
Contact person: Prof. Wolfgang Deppert; -
Imperial College London, United Kingdom
Contact person: Prof. R. Coombes; -
Institute of Tumor Biology/University Medical Center Hamburg-Eppendorf, Germany
Contact person: Prof. Klaus Pantel; -
Lapeyronie Hospital, France
Contact person: Dr. Jean-Pierre Vendrell; -
Medical Center, Leiden University, Netherlands
Contact person: Prof. Hans Tanke; -
Netherlands Cancer Institute, Netherlands
Contact person: Dr. Laura van't Veer; -
University Medical Center Utrecht, Netherlands
Contact person: Dr. Monique Slijper; -
, Germany
Contact person: Dr. Rainer Uhl; -
, Norway
Contact person: Dr. Björn Naume;