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Molecular signatures as diagnostic and therapeutic targets for disseminated epithelial malignancies

Objective

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 pa rtners with long-term expertise in micrometastasis research the DISCOUNT-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 analy sis of circulating tumour DNA and RNA, and expression profiling of tumours are being explored 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 into regional lymph nodes will be analyzed as well as haematogeneous dissemination of DTC via the blood circulation, using bone marrow as an important indicator organ to which epithelial tumour c ells home. Using genomics-based approaches, novel diagnostic target molecules will be identified and validated in functional models. We will complement immunocytochemical 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 revaled by the microarray analysis, and with evaluation of circulating tumour-associated DNA or RNA. Besides the focus on improvement 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 there-fore be analyzed and potential improvements studied. The translation of scientific knowledge into commerical products will be ensured by 3 SMEs with unique technological capabilities.

Call for proposal

FP6-2004-LIFESCIHEALTH-5
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Coordinator

UNIVERSITÄTSKLINIKUM HAMBURG-EPPENDORF
EU contribution
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Address
Martinistr. 52
HAMBURG
Germany

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Participants (13)