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Content archived on 2024-05-29

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

Objective

Translational research of childhood tumours to identify molecular targets for novel generation drugs is urgently needed. Nine European research centres devoted to molecular-biology and pharmacology studies of childhood cancers and two SMEs therefore engaged in the KidsCancer Kinome project. KidsCancer Kinome 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 tumours. Six aggressive childhood tumours (neuroblastoma, medulloblastoma, rhabdomyosarcoma, osteosarcoma, Ewing' tumour and acute lymphocytic leukaemia) will be addressed. These six tumours are responsible for 50% of childhood cancer deaths. Viral shRNA libraries will be applied to test the entire human kinase gene family for tumour-driving kinases in cell lines. They will subsequently be analyzed for mutations and functional parameters in large cohorts of tumour 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 tumour-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 tumour types. KidsCancer Kinome will tribute to a better understanding of the unique paediatric tumour biology and to the development of new drugs.

Fields of science (EuroSciVoc)

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Call for proposal

FP6-2005-LIFESCIHEALTH-6
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Coordinator

INSTITUT GUSTAVE ROUSSY
EU contribution
No data
Address
Rue Camille Desmoulins 39
VILLEJUIF
France

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Total cost
No data

Participants (10)