Objective Cancer remains one of the leading causes of death in the Western world, and while chemotherapy has provided a major improvement in survival for a wide array of malignant diseases lethality remains high in most cancers and side-effects are severe, and include developmental impairment, when used in childhood malignancies, infertility as well as damage to non-malignant tissues with resulting diminished quality of life for a large proportion of survivors.Recently, the realization that several tumour types contain rare populations of cancer stem cells (CSCs), which are capable of reforming the tumour upon transplantation while their progeny are not, have opened the possibility of using CSCs as targets for directed molecular therapies that could lead to improved tumour eradication as well as reduced side effects of treatment. The goal of the present project is to perform a thorough characterization of AML, cALL and breast cancer CSCs, as well as a systematic comparison of these with their normal stem cell and progenitor counterparts using gene profiling, to identify putative molecular targets in CSCs.In parallel, we will use mouse genetic modelling to obtain information about genes regulated by oncogenic changes in stem- and progenitor cell populations. Directly oncoprotein-regulated CSC targets will be validated in vitro and, where relevant, in vivo. Finally, we will screen small molecule libraries for compounds that antagonize leukemogenic oncoproteins in efficient zebrafish models. These compounds will be tested for activity in mammalian assays, screened against the putative targets identified by gene profiling, and used to affinity-purify additional interacting proteins.The final outcome will be a set of identified and validated CSC molecular targets, and a corresponding collection of small molecule inhibitors with activity against the effects of leukemogenic oncoproteins on hematopoietic stem cell/progenitor populations. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncologybreast cancermedical and health sciencesclinical medicinetransplantation Programme(s) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Topic(s) LSH-2005-2.2.0-5 - Exploring the patient's cancer stem cell as a novel therapeutic target Call for proposal FP6-2005-LIFESCIHEALTH-6 See other projects for this call Funding Scheme STREP - Specific Targeted Research Project Coordinator EUROPEAN MOLECULAR BIOLOGY LABORATORY EU contribution No data Address Meyerhofstrasse 1 HEIDELBERG Germany See on map Links Website Opens in new window Total cost No data Participants (5) Sort alphabetically Sort by EU Contribution Expand all Collapse all LUNDS UNIVERSITET Sweden EU contribution No data Address Paradisgatan 5C Box 117 LUND See on map Links Website Opens in new window Total cost No data CANCER RESEARCH UK, LONDON RESEARCH INSTITUTE United Kingdom EU contribution No data Address 61 Lincoln's Inn Fields' 123 LONDON See on map Links Website Opens in new window Total cost No data MEDICAL RESEARCH COUNCIL United Kingdom EU contribution No data Address 20 Crescent Park LONDON See on map Links Website Opens in new window Total cost No data UNIVERSITY OF COPENHAGEN Denmark EU contribution No data Address Norregade 10 2177 COPENHAGEN See on map Links Website Opens in new window Total cost No data SUMMIT CORPORATION PLC United Kingdom EU contribution No data Address 91 Milton Park ABINGDON See on map Links Website Opens in new window Total cost No data