Selecting and validating drug targets from the human kinome for high risk pediatric cancers (KIDSCANCERKINOME)

Basic data for this project

Description

Each year 15,000 European children are diagnosed with cancer and 25% die of this disease. Survivors frequently suffer from late side-effects of current treatments regimes. Translational research of childhood tumors to identify molecular targets for novel generation drugs is therefore urgently needed. In addition, novel targeted drugs currently developed for adult tumors have to become available for children. Indeed, the EU will in 2006 launch a Pediatric Medicines Regulation to stimulate drug evaluation in children. Nine European research centres devoted to molecular-biology and pharmacology studies of childhood cancers and two SMEs therefore engaged in the KidsCancerKinome project. KidsCancerKinome will make a comprehensive analysis of the human protein kinase family. Protein kinases are already excellent targets for many small inhibitory molecules and antibodies designed for adult tumors. Six aggressive childhood tumors (neuroblastoma, medulloblastoma, rhabdomyosarcoma, osteosarcoma, Ewing tumor, acute lymphocytic leukemia) will be addressed, which are responsible for 50% of childhood cancer deaths. Viral shRNA libraries will be applied to test the entire human kinase gene family for tumor-driving kinases in cell lines. They will subsequently be analyzed for mutations and functional parameters in large cohorts of tumor samples. siRNA mediated inactivation in larger cell line panels will critically validate suitable kinases as drug targets. Novel kinase inhibitors being developed for adult oncology will be tested for in vitro activity against the tumor-driving kinases. When no inhibitor is available, a novel generation of siRNA based nucleic acid drugs (LNAs) will be applied. Successful compounds will be taken further to in vivo validation in established xenograft models of the six childhood tumor types. KidsCancerKinome will contribute to a better understanding of the unique pediatric tumor biology and to the development of new drugs. The project gathers 11 European partners and is an European project funded by the European Commission through the 6th Framework Programme for Research and development (FP6-2005-LIFESCIHEALTH-6037390) - www.cordis.lu/fp6. The sixth framework programme covers community activities in the field of research, technological development and demonstration (RTD) for the period 2002 to 2006. It is a collection of the actions at EU level to fund and promote research. In addition, KidsCancerKinome gathers the 9 ITCC research laboratories. ITCC (Innovative Therapies for children with cancer - http://www.itcc-consortium.org) has been set up in 2003. ITCC integrates a clinical and pre-clinical European research framework in paediatric oncology. ITCC biology consists of a consortium of 9 European research laboratories, who have set up a rational step - wise pre-clinical target identification and drug evaluation system to select and prioritize anti-cancer compounds.